Soft Tissue Sarcoma

Presentor : Dr Ajit H
Moderator : Dr Praveen M
- Sarcomas represent a heterogenous group of
rare malignant tumours

- Mesenchymal origin

- Occur anywhere

- Account for less than 1% of malignant tumours

- Sarcomas include more than 70 histologic
subtypes

- Extermity is the most common location ( 50-

60%) , followed by trunk (19%)

- Then retroperitoneum (15%) and head and

neck (9%).
 History
- In 1761 , Giovanni Battista Morgagni, an
Italian anatomist reported first case of
retroperitoneal sarcoma(RPS)- a large
lipomatous tumour during the autopsy of a 60-
year-old female
Retroperitoneum divided into three spaces –

- Anterior pararenal space

- Perirenal space

- Posterior pararenal space

Anterior pararenal space:

- It is anterior to renal fascia , but posterior to

peritoneum

- Contains the ascending and descending colon,

the duodenum, and the pancreas.
Perirenal space :

- Lies posterior to anterior pararenal space

- Contains inferior vena cava, the aorta, kidneys,

and adrenal glands.
Posterior pararenal space :

- Posterior pararenal space is in continuity with

preperitoneal fat of the anterior abdomen.
 Why surgeons need to know?
- High rates of recurrence and poor overall
survival.

- The overall 5-year survival rate is 33% to 39%

and at least 70 % of cases will relapse

- Most succumb to lung metastasis - within 2 to

3 years after initial diagnosis
 Subtypes of STS and frequencies
SUBTYPES PERCENTAGE

Liposarcoma 15

Leiomyosarcoma 12

Unclassified sarcoma 11
Synovial sarcoma 10

Malignant peripheral nerve 6

sheath tumor

Rhabdomyosarcoma 5

Fibrosarcoma 3

Ewing sarcoma 2
Angiosarcoma 2

Osteosarcoma 1

Epithelioid sarcoma 1

Chondrosarcoma 1

Clear cell sarcoma 1

Alveolar soft part sarcoma 1

Malignant hemangiopericytoma 0.4

 Epidemiology
• 1) Radiation exposure :
It is a rare but well established risk factor with a risk
of 8 to 50 times greater than the general-population.

The most common histologic types were osteogenic

sarcoma, pleomorphic undifferentiated sarcoma,
angiosarcoma, and lymphangiosarcoma
• 2) Occupational exposure :
Herbicides such as phenoxyacetic acids and to
wood preservatives containing chlorophenols –
increase risk

Others: thorium oxide (Thorotrast),

vinylchloride, and arsenic - hepatic
angiosarcomas
• 3) Trauma :
Patient often give a history of trauma
No causal relationship identified
The most frequent retroperitoneal sarcoma
subtypes are
1) Liposarcoma

2) Leiomyosarcoma

3) MFH( malignant fibrous histiocytoma) –

currently referred as undifferentiated pleomorphic
sarcoma.
• LIPOSARCOMA
- Most common retroperitoneal sarcoma subtype

- Appears as large sized , well rounded mass

with homogenous fatty content

- Pathogenesis : amplification of chromosome

12q leading to upregulation of MDM2 and
CDK4
• Divided into

1) Locally aggressive – well differentiated type

2) Malignant type – dedifferentiated ,

pleomorphic, myxoid and round cell type
• Well differentiated and dedifferentiated :
retroperitoneum location

• Pleomorphic, myxoid and round cell type:

extremity location
• LEIOMYOSARCOMA :
- Highly metastasizing smooth muscle
malignant tumour

- Most common site : retroperitonuem( Inferior

Vena Cava below level of heptic vein) ,
peritoneal cavity (uterus)

- Appears as heterogenous , well circumscribed

tumour with cystic or necrotic central area
• Usually in 6th to 7th decade of life

• Etiology : radiation exposure and Epstein Barr

virus

• Stains positive for Desmin, Smooth muscle

actin
 Molecular pathogenesis
Sarcomas can be divided into 3 groups

Based on genetic events leading to development

1) Specific translocations or gene amplification
2) Defining oncogenic mutations
3) Complex genomic rearrangements
1) Translocation – associated sarcomas :
Account for 20-30% sarcomas

Examples : Ewing’s sarcoma, Clear cell sarcoma

, Myxoid/round cell liposarcoma , Alveolar
rhabdomyosarcoma, Desmoplastic small round
cell tumor , Synovial sarcoma
• 2) Amplification associated sarcomas:

Oncogenes such as MDM2, N-myc, c-erbB2,

and members of the ras family involved

Example : Dedifferentiated liposarcoma

• 3) Oncogenic mutations :

- Example – gastrointestinal stromal tumours –

- Single point mutation in gene encoding gene
encoding KIT receptor tyrosine kinase or
platelet-derived growth factor receptor-α
(PDGFRA)
4) Complex genomic rearrangements
Neurofibromatosis type 1
• 10% risk- malignant peripheral nerve sheath
tumor
Li- Fraumeni syndrome
• Risk of rhabdomyosarcoma, undifferentiated
pleomorphic sarcoma, and pleomorphic
sarcoma
 Familial adenomatous polyposis
• Risk of developing desmoid tumour
 Initial assessment
• Clinical behavior determined by –

1) Histologic subtype

2) Grade of aggressiveness

3) Size
- Average age at presentation : 54 years

- Male and Female ratio : 1:1

- Main pathway of metastasis : hematogenous to

the lungs
Clinical features –
- Mainly asymptomatic

- If symptoms present , variable presentation

and includes : abdominal pain, weight loss,
early satiety, nausea, vomiting , back or flank
pain, paresthesias, and weakness.
- Testicular examination in men

- Differential diagnosis :
1) Benign lipoma ( 100 times more common)

2) Retroperitoneal lymphadenopathy: lymphoma,

germ cell tumor, or metastasis from
gastrointestinal primary

3) Hematoma
Staging – American Joint Committee- 2018
Primary tumour ( T)

Primary tumor cannot be assessed TX

No evidence of primary tumor T0

Tumor 5 cm or less in greatest dimension T1

More than 5 cm and less than or equal to T2

10 cm in greatest dimension
More than 10 cm and less than or equal to T3
15 cm in greatest dimension
More than 15 cm in greatest dimension T4
Regional Lymph Nodes (N)

Regional lymph nodes cannot be assessed NX

No regional lymph node metastasis N0

Regional lymph node metastasis N1

Distant metastasis ( M)

No distant metastasis M0

Distant metastasis M1
Definition Mitotic count

0-9 mitoses per 10 HPF 1

10-19 mitoses per 10 HPF 2

≥20 mitoses per HPF 3

Definition Necrosis score

No necrosis 0
≤ 50% tumour necrosis 1
≥ 50% tumour necrosis 2
Definition Differentiation
score

Sarcomas closely resembling normal adult mesenchymal tissue 1

Sarcomas for which histologic typing is certain 2

Embryonal and undifferentiated sarcomas, sarcomas of doubtful 3

types , synovial sarcomas, soft tissue osteoarcoma, Ewing
sarcoma/ primitive neuroectodermal tumour of soft tissue
 FNCLCC(Fédération Nationale des Centres
de Lutte Contre Le Cancer) Histologic grade

G G DEFINITION

GX Grade cannot be assessed

G1 Total differentiation, mitotic count, necrosis score – 2 or 3

G2 Total differentiation, mitotic count, necrosis score – 4 or 5

G3 Total differentiation, mitotic count, necrosis score – 6,7,8

 AJCC prognostic stage grouping
T N M GRADE STAGE
T1 N0 M0 G1,GX IA

T2, T3, T4 N0 M0 G1,GX IB

T1 N0 M0 G2,G3 II

T2 N0 M0 G2,G3 III A

T3, T4 N0 M0 G2,G3 III B

ANY T T1 M0 ANY G III B

ANY T ANY N M1 ANY G IV

 Imaging studies
• Ultrasound
Advantages :
- inexpensive
- in patients with metallic implants
- adjunct to MRI when findings are
indeterminate and for delineating adjacent
vascular structures
-postoperative surveillance and to guide
biopsies.
• Disadvantage :

- low inter- and intra-observer agreement

- operator’s technique related skills.

 Computed Tomography
It is the preferred imaging technique for
retroperitoneal sarcoma
1) Identify and characterize the masses in terms
of location, size and extension in the
retroperitoneal space

2) Spectrum of differential diagnosis

(solid/cystic, neoplastic/nonneoplastic)
3) Guide the percutaneous biopsy

4) Plan surgery for complete surgical resection -

local soft tissue infiltration and relationship with
critical neurovascular structures

5) Identify postoperative complications

6) Assessing response to neoadjuvant treatment

7) Follow-up and restaging

Also a CT chest is to be done – lung metastasis

When ? At presentation and before radical
treatment
• Liposarcoma :

- Differentiated liposarcoma : smooth margins

with lobular contour , thick septa , nodular
component with low contrast enhancement
- Dedifferentiated liposarcoma :
- Non lipomatous mass surrounded by fatty
tissue
- Calcifications present
- Nodular or irregularly linear septa within the
lesion
- Increase enhancement after contrast
• Leiomyosarcoma:
Large mass with well defined margin iso
attenuating to muscle

In contrast enhancement- arterial phase shows

feeding vessels and peripheral enhancement
 Fluorine-18 deoxyglucose positron
emission tomography( FDG-PET /CT)
• Advantage :
1)Detect primary and recurrent soft tissue lesions

2) Define the spread of neoplasm

3) Exclude pulmonary metastasis/ multifocal

intra-abdominal disease
4) Assess early treatment response

5) For biopsy
• Disadvantage :

1) No clear role for diagnosis

2) Poor discrimination between low-grade

tumors and benign lesions
 Biopsy examination
- CT-guided core needle biopsy is appropriate to
provide a tissue diagnosis

- But not mandatory

- Also sampling bias – giving false information

 Treatment
- For localized sarcoma- Complete surgical
resection is the mainstay of treatment

- To improve local control and potentially

overall survival- extended surgical approach (en
bloc tumor resection with adherent organs and
structures) advocated
 Extent of resection
- Before going for multivisceral resection – a
balance between margin adequacy and morbidity
should be considered

- Generally , en bloc resection of ipsilateral

colon, kidney, adrenal, and psoas muscle is done
to get a negative margin
- In some patients , resection of pancreas and
spleen or a pancreaticoduodenectomy or
vascular resection is required

- Surgical access : a midline incision is the most

common

- For better exposure and vascular control-

transverse/ oblique extension or
thoracoabdominal incision
(1) Midline laparotomy incision

(2) Subcostal extension

(3) Extension transversally to the flank

(4) Ilioinguinal incision

(5) Right thoraco-phreno-laparotomy

• Leiomysarcoma :
- Surgical resection with negative margin is first
line of therapy

- If metastasis present , non resectable:

- Olaratumab (PDGFR alpha antibody ) +
Doxorubicin
 Role of radiotherapy
- Complex

- Tumours are large and close to radiosensitive

structures

- Several techniques used : preoperative and

postoperative external-beam radiation therapy,
intraoperative radiation therapy, brachytherapy
• Pre op radiation therapy

- Better tolerated as toxic effects are less

- Tumor borders are definable

- Tumor displaces radiosensitive viscera away

from the treatment field
- Effective doses of radiation may be lower
preoperatively

- Thus, for patients with large, high-grade tumors

or recurrent low-grade tumors :
Total pre-op dose of 50 Gy followed by surgical
resection is considered
 Role of chemotherapy
- Controversial

- As the trials are inconclusive on the role of

chemotherapy and no consclusions can be drawn
(European Society for Medical Oncology ,
European Organisation for Research and
Treatment of Cancer-Soft Tissue and Bone
Sarcoma Group)
 Treatment of recurrence
- Recurrence rates are high .

- Eg ; Retroperitoneal leiomyosarcomas- recur

locally and metastasize to the lungs and liver.

- Retroperitoneal sarcomas recur diffusely

throughout the peritoneal cavity
- Treatment : extended surgical resection

- But probability of resectability declines with

each recurrence.
 Metastatic sarcomas

- First-line therapy : Single or combination

therapy with anthracyclines

- Second-line therapy : gemcitabine and

docetaxel
 Immunotherapy agents
- Use of immunotherapy agents – fail to give
good results

- But , undifferentiated pleomorphic sarcoma or

dedifferentiated liposarcoma have response
when treated with pembrolizumab, a
programmed death-1 inhibitor.
- Other Novel agents are undergoing further
study such as trabectedin, tyrosine kinase
inhibitors, MDM2 antagonists, peroxisome
proliferator-activated receptor gamma agonists,
and CDK4 antagonists.
 Studies
In 1954 Pack and Tabah , 120 patients treated for
retroperitoneal tumors at the Memorial Sloan
Kettering Cancer showed results :

- Complete excision of the tumor was achieved

in 21% of cases

- Operative mortality of 10.8%

In 1973, Kinne published results of 34 RPS at
the Memorial Hospital for Cancer and Allied
Diseases of New York.
- 32.4% : complete resection with/without
radiation therapy
- 44.1% : partial resection and radiation therapy
- 23.5% : biopsy and radiation therapy.

- Operative mortality was 11.7%.

In 1984, McGrath published results for 47 RPS
patients who underwent surgery at the Medical
College of Virginia.

- Complete resection was performed in 38% of

patients

- In 68% of cases, curative surgery required

multivisceral resection
- Kidney (32%), colon (25%) and adrenal gland
(18%) : most commonly resected

-The complication rate was up to 32%;

In 1998, Lewis et al demonstrated that the
overall survival was better with complete
resection in a study of 500 patients treated over
a 15-year period with a postoperative mortality
rate of 4%
HPR showed : dedifferentiated liposarcoma
pT4NxMx . Stage IIIB
• References
1) Sabsiton textbook of surgery 21 st edition
2) Schwartz’s principles of surgery 11 th edition
3) Current treatment of retroperitoneal sarcomas-
a joint effort with the Italian society of surgical
oncology- 2018 EDITION
4) Fischer’s master of surgery 6th edition
• THANK YOU