This document discusses soft tissue sarcomas (STS), a rare type of cancer that arises in connective tissues like muscles or fat. It notes that STS account for about 1% of adult cancers in the US, with most occurring in extremities or trunk. Risk factors include radiation exposure, certain chemicals, and genetic conditions. STS are classified and graded based on cell type and differentiation. Treatment typically involves surgical resection with clear margins, sometimes combined with radiation or chemotherapy depending on stage, grade, and location. Prognosis depends on stage and grade, with 5-year survival rates ranging from 54-65% after complete resection of primary retroperitoneal sarcomas.

1. Dr. Joseph A. Di Como

2. Introduction
Group of anatomically and histologically diverse
tumors of extraskeletal mesenchymal origin.
Rare: Account for about 1% of adult malignancies and
approximately 9,000 to 12,000 cases reported every
year in the United States
3,000 to 4,000 deaths annually from STS in the
United Stated

3. Location and Type

4. Etiology
History of radiation therapy increases risk, grade of
tumors and risk for metastasis.
Chemical exposure
 Thorotrast, vinyl chloride, arsenic for hepatic angiosarcoma
Genetic syndromes
 Neurofibromatosis – nerve sheath tumors
 Li Fraumeni Syndrome (germline mutation in p53)
 Hereditary retinoblastoma (germline mtuation in Rb)
 Familial adenomatous polyposis/Gardner’s syndrome
 Familial gastrointestinal stromal tumor syndrome – KIT mutation
 Skin hyperpigmentation, uticaria, cutaneous mast cell dx

5. Classification
Soft tissue and bone
 viscera (gastrointestinal, genitourinary, and gynecologic organs)
 nonvisceral soft tissues (muscle, tendon, adipose, pleura, and connective tissue)
By differentiation (usually with IHC staining)
 adipocytic tumors
 fibroblastic/myofibroblastic tumors
 fibrohistiocytic tumors
 smooth muscle tumors
 pericytic (perivascular) tumors
 primitive neuroectodermal tumors (PNETs)
 skeletal muscle tumors
 vascular tumors
 osseous tumors
 tumors of uncertain differentiation

7. Biopsy
Most present as painless mass leading to delayed diagnosis
– Mistaken for lipoma, hematoma, muscle injury
Core needle biopsy guided by palpation or by image
guidance if not palpable
 Few cases of tumor seeding with closed biopsy so some recommend
tattooing site for later excision with specimen
Excisional biopsy for superficial small lesions if needle
biopsy non-diagnostic
Incision biopsy
 Longitudinal incision without tissue flaps with meticulous hemostasis
to prevent tumor seeding in hematomas
 Send biopsy fresh and orientated

8. Imaging
MRI
 For extremity masses
 Gives good delineation between muscle, tumor and blood
vessels
CT for abdominal and retroperitoneal
PET
 May help determine high vs. low grade
 May be helpful in recurrences

9. Staging
AJCC/UICC Staging System for Soft Tissue Sarcomas
 T1: <5cm
 T1a: superficial to muscular fascia
 T1b: Deep to muscular fascia
 T2: >5cm
 T2a: superficial to muscular fascia
 T2b: Deep to muscular fascia
 N1: Regional nodal involvement
 Grading
 G1: Well-differentiated
 G2: Moderately differentiated
 G3: Poorly differentiated
 G4: Undifferentiated

10. Staging
Stage IA G1,2 T1a,b N0 M0
Stage IB G2,2 T2a,b N0 M0
Stage IIA G3,4 T1a,b N0 M0
Stage IIB G3,4 T2a N0 M0
Stage III G3,4 T2b N0 M0
Stage IV Any G Any T N1 M1
**Does not take into account extremity vs. visceral
Staging system predicts survival and risk of metastasis, but not local recurrence

11. Survival by stage

12. Relative risk for recurrence and survival
Age >50 years 1.6
Local recurrence at presentation 2.0
Microscopically positive margin 1.8
Size 5.0–10.0 cm 1.9
Size > 10.0 cm 1.5
High-grade 4.3
Deep location 2.5
Local recurrence 1.5

13. Surgery
Limb-sparing vs amputation
 Comparison study with post-op radiation in limb sparing
showed no difference in survival
Amputation still may be indicated for neurovascular
or bone involvement

14. Resection
Arbitrary 2 cm margin if no plan for post-op
radiotherapy
Negative margins may be adequate for post-op
radiation therapy
 Presence of positive margins increases local recurrence by 10-
15%
No need for lymph node dissection as only 2-3% have
nodal metastasis

15. Adjuvant radiotherapy
Small, low grade tumors resected with 2 cm margins
may not require radiation
Improves local control but not survival
Whether improved local control leads to improved
survival is controversial

16. Local recurrence with post-op brachytherapy

17. Pre-op or post-op radiation?
Some avoid pre-op use because of increased wound
complications (although this is debatable)
 RCT looking at wound complication rate pre-op vs post-op
radiation showed 35% vs 17%
 Risk confined to lower extremity
 Conclusions: pre-op may be better for upper extremity and
head & neck because of equal wound complication risk and
benefit of lower radiation doses to more vital tissues

18. Pre-op vs post-op radiotherapy

19. Chemotherapy
Can improve local control, but not survival
Doxorubicin and ibosfamide have response rates of
20%
Use only in advanced disease
Combination with radiation or neoadjuvant therapy
are controversial
Hypothermic isolated limb perfusion may be used for
palliation

20. Treatment of Recurrence
20-30% of STS patients will recur
More common in retroperitoneal and head & neck
high grade tumors because hard to get clear margins
 38% for retroperitoneal
 42% for head and neck
 5-25% for extremity
After re-resection recurrence is 32% for extremity and
much higher for visceral

21. Metastatic disease
Lung most common site of mets, but visceral often go
to liver
Median survival from development of metastatic
disease is 8-12 months
Resection of pulmonary mets can give 5 year survival
of 32% if all mets can be removed
 >3 mets is poor prognosticator

22. Case #1
64 y/o male with increasing abdominal girth

23. Retroperitoneal Sarcomas
15% of all sarcomas
Liposarcoma 42% and leiomyosarcoma 26%
CT scan can show cystic/solid/necrotic components and relation to
surroundings
CXR to r/o mets, chest CT if CXR abnormal
Biopsy not necessary unless suspect a lymphoma or germ cell tumor
or plan preop chemo or radiation
En bloc resection is standard treatment
 bowel prep
 assess bilateral kidney function
 50-80% need organ resection
 78% of primary lesions can be completely resected

24. Liposarcoma

25. Survival after resection of primary
retroperitoneal sarcoma

26. Prognosis for retroperitoneal sarcomas
5 year survival after complete resection of 54-65%
 Drops to 10-36% if incompletely resected
Recurrence occurs in 46-59% of completely resected
tumors

27. Radiation or chemotherapy for retroperitoneal
sarcomas
Radiation
GI and neurotoxicities limit delivery of sufficient doses
May improve local control
Recommended for use only in clinical trials given lack
of data either way
Chemotherapy
Use for recurrent, unresectable or metastatic disease

28. Case #2
• 49 y/o female with GERD undergoing EGD

29. GIST
Separate subtype of sarcoma defined by expression of c-
Kit (CD117)
Surgery: complete resection without local or regional
lymphadenectomy
Very resistant to traditional chemotherapy
Gleevec (imantinib mesylate)
 c-Kit is constitutively active tyrosine kinase receptor
 Drug is tyrosine kinase inhibitor used in CML
 Initial studies showed 54% response rates
 Two RCTs currently looking at adjuvant treatment

30. GIST

31. GIST

32. Extremity sarcomas
MFH
Synovial sarcoma

33. Breast sarcomas
1% of all breast neoplasms
Wide excision with negative margins
No clear role for adjuvant radiotherapy

34. Sarcoma after mastectomy

35. Vascular sarcomas
Angiosarcoma, hemangiosarcoma,
lymphangiosarcoma, hemangiopericytoma
Key points:
 Hepatic angiosarcoma – thorotrast, vinyl chloride, arsenic
 Stewart Treve’s – lymphangiosarcoma in chronic
lymphedema
High risk for bleeding during excision
No clear role for chemo or radiation

36. References
www.Dartmouth-Hitchcock.org
The Johns Hopkins ABSITE Review Manual. By
Robert A. Meguid, Kyle Van Arendonk, Pamela A.
Lipsett