Sarcoma - Mussa Mensa

Sarcoma teaching

1. Mussa Mensa
CT2
The Welsh Centre
for Burns & Plastic
Surgery
Sarcoma

2. Epidemiology
Histopathology
Clinical presentation
Investigation
Staging and grading
Management
Prognosis
Overview

3. Sarcomas are a diverse group of rare tumours, accounting for less than
1% of all malignant tumours
1
Arise from the embryonic mesoderm
Introduction
Ectoderm  nervous
system, epidermis (muscle
+ connective tissue in
the head)
Mesoderm 
connective tissue,
muscle (except
head)
Endoderm
epithelial, glands

4. Sarcomas are a diverse group of rare tumours, accounting for less than
1% of all malignant tumours
1
Arise from the embryonic mesoderm
They present most commonly as an asymptomatic mass originating in an
extremity, but can occur elsewhere in the body
 Although rare, half of those diagnosed will die from the sarcoma
2
Introduction

5. Incidence varies  1.8 – 5 cases per 100,000 per year
In the UK ≈1500-2000 cases diagnosed annually
1
Incidence increases with age – average age at diagnosis ≈57.4 years
3
Certain subtypes e.g. rhabdomyosarcoma more common in children
Men and women are equally affected
3,4
Epidemiology

6. The various sarcomas include:
bone sarcomas (osteosarcomas and chondrosarcomas),
Ewing's sarcomas,
peripheral primitive neuroectodermal tumors,
soft tissue sarcomas (STS) - most frequent
Sarcoma Types

7. The various sarcomas include:
bone sarcomas (osteosarcomas and chondrosarcomas),
Ewing's sarcomas,
peripheral primitive neuroectodermal tumors,
soft tissue sarcomas (STS) - most frequent
STS can occur anywhere in the body, but most originate in the following:
lower extremity (thigh, buttock, groin) (46%)
trunk (18%)
upper extremity (13%)
the retroperitoneum (13%),
the head and neck (9%)
Usually differentiate towards one tissue type
The WHO has defined more than 50 histological subtypes
Sarcoma Types

8. Table 1 – the main histological subtypes and line of differentiation
Sarcoma Types
Sarcoma Normal
counterpart
Percentage of
STS
Malignant fibrous
histiocytoma
Fibroblast or
myofibroblast
≈28%

9. Malignant fibrous histiocytoma (MFH):
Formerly known as fibrosarcoma, and more recently classified as
pleomorphic undifferentiated sarcoma (PUS)
Most common type of STS
Aggressive biological behaviour and poor prognosis
Sarcoma Types

10. Malignant fibrous histiocytoma (MFH):
Formerly known as fibrosarcoma, and more recently classified as
pleomorphic undifferentiated sarcoma (PUS)
Most common type of STS
Aggressive biological behaviour and poor prognosis
Sarcoma Types

11. Malignant fibrous histiocytoma (MFH):
Formerly known as fibrosarcoma, and more recently classified as
pleomorphic undifferentiated sarcoma (PUS)
Most common type of STS
Aggressive biological behaviour and poor prognosis
Typically occur in the retroperitoneum and proximal extremities, and
occasionally in bone
Macroscopically - typically large (5-20 cm), well circumscribed but
unencapsulated, with a grey firm heterogeneous cut surface, sometimes
with areas of necrosis
Sarcoma Types

12. Malignant fibrous histiocytoma (MFH):
Formerly known as fibrosarcoma, and more recently classified as
pleomorphic undifferentiated sarcoma (PUS)
Most common type of STS
Aggressive biological behaviour and poor prognosis
Typically occur in the retroperitoneum and proximal extremities, and
occasionally in bone
Macroscopically - typically large (5-20 cm), well circumscribed but
unencapsulated, with a grey firm heterogeneous cut surface, sometimes
with areas of necrosis
Sarcoma Types
Daigeler et al. BMC Surgery 2006 http://radiopaedia.org/

13. Microscopically - poorly differentiated fibroblasts, myofibroblasts,
histiocyte-like cells with significant cellular pleomorphism, storiform
architecture and also demonstrate bizarre multi-nucleated giant cells
Sarcoma Types
Malignant fibrous histiocytoma (MFH):
Formerly known as fibrosarcoma, and more recently classified as
pleomorphic undifferentiated sarcoma (PUS)
Most common type of STS
Aggressive biological behaviour and poor prognosis
Typically occur in the retroperitoneum and proximal extremities, and
occasionally in bone
Macroscopically - typically large (5-20 cm), well circumscribed but
unencapsulated, with a grey firm heterogeneous cut surface, sometimes
with areas of necrosis
6

14. Table 1 – the main histological subtypes and line of differentiation
Sarcoma Types
Sarcoma Normal
counterpart
Percentage of
STS
Malignant fibrous
histiocytoma
Fibroblast or
myofibroblast
≈28%
Liposarcoma Adipocyte ≈15%

15. Liposarcoma:
Malignant tumours of fatty tissue and are the malignant counterpart to a
benign lipoma
They are the second commonest type of soft-tissue sarcoma
Age at diagnosis ≈40-60 years
Usually occur at the extremities or in the retroperitoneum
Sarcoma Types
https://grosspathology-sites.uchicago.edu/lipoma http://radiopaedia.org/

16. Liposarcoma:
Originate from mesenchymal cells, they are classified histologically into 5
types
I.well differentiated liposarcoma – commonest (≈50%); low grade
II.myxoid liposarcoma – 2
nd
commonest; intermediate grade
III.round cell/de-differentiated liposarcoma
IV.Pleomorphic liposarcoma – least common
V.mixed
Sarcoma Types
I - WDLS
III - DDLS
IV - PMLSII - MXOLS
7

17. Table 1 – the main histological subtypes and line of differentiation
Sarcoma Types
Sarcoma Normal
counterpart
Percentage of
STS
Malignant fibrous
histiocytoma
Fibroblast or
myofibroblast
≈28%
Liposarcoma Adipocyte ≈15%
Leiomyosarcoma Smooth muscle ≈12%

18. Leiomyosarcoma:
Malignant neoplasms that originate from smooth muscle cells
May be considered the malignant counterpart of a leiomyoma (most
common = uterine leiomyoma/fibroid)
Can potentially occur anywhere where there is smooth muscle. Commonly
described sites include:
uterus: uterine leiomyosarcoma: most common
retroperitoneum: retroperitoneal leiomyosarcoma; most common non-uterine
site
stomach - gastric leiomyosarcoma (GIST)
Other less common sites include the oesophagus, small intestine, liver,
bladder, nasopharynx, bone, venous structures (IVC/renal vein), spermatic cord
Sarcoma Types

19. Leiomyosarcoma:
Macroscopic appearance - bulky, invasive masses which are often
necrotic and hemorrhagic
Sarcoma Types
http://radiopaedia.org/
http://goo.gl/WF0les

20. Leiomyosarcoma:
Macroscopic appearance - bulky, invasive masses which are often
necrotic and hemorrhagic
Microscopically – well differentiated vs poorly differentiated
well differentiated = similar to leiomyomas/native smooth muscle tissue with
little atypia
poorly differentiated = atypia, pleomorphism, increased mitotic rate +/-
necrosis
Sarcoma Types
http://goo.gl/1hb7nO
normal
myometrium
leiomyoma leiomyosarcoma
http://goo.gl/uk1Up9

21. Table 1 – the main histological subtypes and line of differentiation
Sarcoma Types
Sarcoma Normal
counterpart
Percentage of
STS
5
Malignant fibrous
histiocytoma
Fibroblast or
myofibroblast
≈28%
Liposarcoma Adipocyte ≈15%
Leiomyosarcoma Smooth muscle ≈12%
Synovial sarcomaUnknown ≈10%
Malignant peripheral
nerve sheath tumour
Schwann cell ≈6%
RhabdomyosarcomaSkeletal muscle ≈5%
Angiosarcoma Endothelial cell≈2%
Ewing’s sarcoma Unknown ≈2%

22. Most sarcomas seem to arise de novo with no obvious cause
Cytogenetic analysis has identified several oncogenes and chromosomal
translocations associated with certain histologic subtypes
Mutations in tumour suppressor genes e.g. Rb gene or p53 gene can lead
to the development of (retinoblastomas and) sarcomas of soft tissue and
bone
P53 gene mutations observed in 30-60% of STS
5
Aetiology

23. High incidence of sarcomas in those with hereditary/germline mutations
of p53 gene e.g. Li-Fraumeni syndrome
Radiation induced STS rare but has been associated with RTx for breast
cancer and lymphoma
Exposure to chemical carcinogens e.g. vinyl chloride, associated with
increased incidence
1
Aetiology

24. Soft tissue swellings are common, most are benign
Typically present with a painless mass growing slowly for months or years
Function and general health usually not affected, hence may be found
incidentally
Size at presentation depends on location – extremities = small when
discovered; retroperitoneal = large before apparent
DDx includes - lipomas, lymphangiomas, leiomyomas, and neuromas;
primary or metastatic carcinoma, melanoma, or lymphoma
History and presentation + rarity of sarcomas commonly leads to initial
misdiagnosis
Clinical Presentation

25. O/E – important to ascertain the following:
size, anatomical site + ?painful
?fixed to the skin
?beneath the skin but margins easily defined
?tethered + accentuated by muscle contraction i.e. beneath deep fascia
Depth of tumour is a sensitive marker of malignancy
8
Table 2:
Clinical Presentation
Department of Health criteria for urgent
(2WW) referral of a soft tissue lesion
Soft tissue mass >5cm (golf ball size)
Painful lump
A soft tissue lump that is increasing in size
A lump of any size that is deep to muscle fascia
Recurrence of a lump after previous excision

26. NICE guidelines
9
recommend that patients with suspected soft tissue
sarcoma are “urgently referred for rapid assessment at a one-stop
diagnostic clinic” where triple assessment can be undertaken
clinical history & examination
ultrasound imaging + specific imaging
tissue biopsy
Investigation

27. Plain radiography:
lumps in the extremities; rule out mass arising from bone
certain subtypes e.g. synovial sarcoma show
characteristic calcification
Ultrasound:
rapid triage of benign vs supicious lesions
useful when clinical suspicion exists but referral criteria
not met
should not delay referral for lesions with a high degree of
clinical suspicion for malignancy
US guided biopsy
investigation
http://goo.gl/oQ8FNI
http://goo.gl/zlm0wz

28. CT and MRI:
MRI is preferred as the initial imaging modality for STS of the extremities,
trunk and head & neck
CT = gold standard for preoperative staging + used to assess intra-
abdominal masses
HRCT has a role in identification of bony involvement + exclusion of
pulmonary metastasis
No difference in the two for efficacy of local staging of STS in the
extremities
Advantage of MRI is multiplanar images with better spatial orientation
investigation

29. Biopsy:
Core needle biopsy
advantages = sensitivity of 90-95%, quicker, cheaper and safer (0.4% vs 12-
17% complication rate
1
) than open incision biopsy
disadvantages = several cores needed to improve accuracy; image guidance
for deeper/necrotic tumours
FNAC – not recommended; lower accuracy than core biopsy
NICE guidelines
9
recommend that results should be interpreted by a
specialist sarcoma pathologist
investigation

30. Tumour staging can help estimate prognosis and survival as well as plan
management
Several systems are used to stage STS
The most widely accepted are the:
American Joint Comitte on Cancer grading system
International Union Against Cancer staging system
Staging

31. American Joint Comitte on Cancer grading system - Table 3
Staging
Grade Characteristic
Tumour (T)
T0 No evidence of primary tumour
T1 Primary tumour <5cm (T1a = superficial; T1b = deep)
T2 Primary tumour >5cm (T2a = superficial; T2b = deep)
Regional lymph nodes (N)
N0 No regional lymph nodes
N1 Regional lymph nodes involved
Metastases (M)
M0 No metastases
M1 Distant metastases

32. International Union Against Cancer staging system – Table 4
Staging
StageTumour characteristics AJCC
equivalent
1A Low grade, small, superficial or deepT1 a-b, N0, M0
1B Low grade, large, superficial T2a, N0, M0
II A Low grade, large, deep T2b, N0, M0
II B High grade, small, superficial or deepT1 a-b, N0. M0
II C High grade, large, superficial T2a, N0, M0
III High grade, large, deep T2b, N0, M0
IV Any metastasis Any T, N1 or M1

33. Tumour grade is related to
prognosis
A commonly adopted system in
the UK is the Trojani grading
system
High grade tumours are poorly
differentiated or undifferentiated
They carry a high likelyhood of
metastasis and poor patient
survival
Tumour grade is the most
important prognostic factor in
metastatic recurrence
grading

34. Aims:
Ensure long term survival
Avoid local recurrence
Maximise patient function whilst minimising morbidity
Requires an MDT approach with various combinations of surgery,
radiotherapy and chemotherapy
9
Treatment decisions best made by an MDT consisting of surgeons,
pathologists, radiologists, medical oncologists and clinical oncologists
Take into account the tumour’s site and stage plus the patient’s
comorbidities and treatment preferences
Management

35. Surgery is the mainstay of treatment for patients with localised disease
Aims to excise the tumour completely along with a biological barrier of
normal tissue
No international consensus exists on what constitutes an acceptable
resection margin
UK consensus guidelines state that 1cm of normal soft tissue or
equivalent (e.g. fascia) is an acceptable margin
10
Positive margins carry an increased risk of disease recurrence and
reduced disease specific survival
Surgical management

36. The standard of care for most patients with STS of the extremities is ‘limb
salvage surgery’
Aims to retain a functional limb to maintain a postop quality of life +
acceptable resections margins to ensure low risk of recurrence
Improved adjuvant radiotherapy + reconstructive surgery have enabled
more limited surgery to be performed and function to be preserved
Advances in reconstructive techniques have enabled limb preservation in
complex cases
European Society of Medical Oncology guidance states that treatment by
wide surgical excision if sufficient for low grade T1a/T1b + superficial high
grade tumours
Surgical management

37. Surgical management
Early complications of surgery include haemorrhage, wound infection, VTE
and flap failure
Postop rehab varies with patient and type of surgery – intensive specialist
nursing, physiotherapy and occupational therapy often required
1

38. RTx has been shown to improve local control in surgically resectable
disease
Candidates for Rtx include:
intermediate or high grade STS
large, deep low grade sarcomas
incompletely resected tumours close to important structures
Optimal time for RTx unclear – in the UK postop RTx is the standard
Complications associated with postop RTx include joint stiffness, oedema
and pathological fractures
Radiotherapy

39. UK consensus guidelines
10
do not advocate chemotherapy as standard
management
There is conflicting evidence in the use of adjuvant chemotherapy in the
management of STS of the extremities
Chemosensitivity varies with histological subtypes e.g.myxoid liposarcoma
are more chemosensitive than some other types
In cases of advanced disease, use of palliative adjuvant chemotherapy
may be appropriate e.g.
in those with large and highgrade tumours (typically synovial sarcoma and
liposarcoma)
aim to shrink the tumour prior to palliative surgery
Chemotherapy

40. Isolated limb perfusion
Widely used in Europe to treat
STS of the extremities, but only
in a few UK centres
High concentrations of
chemotherapeutic agents are
delivered under hyperthermic
conditions
Via arterial and venous cannula to a limb isolated by
pneumatic tourniquet compression
Can be used to reduce tumour size to enable limb
salvage procedures or for palliative treatment
Limb salvage rates as high as 74-87% in selected patients with
intermediate or high grade disease

41. 40-50% of patients with soft tissue sarcoma develop metastatic disease
Common sites of metastases include: lung, local soft tissues, local and
distant lymph nodes
≈20% of patients with STS of the extremities have isolated pulmonary
metastases
The outlook for metastatic disease is poor (estimated 5 year survival of
8% with pulmonary metastases, 59% with lymph node metastases)
1
Restaging once mets discovered is important in planning subsequent
management
Isolated/single organ mets may be managed surgically +/- adjuvant
treatment
metastases

42. Rationale = early recognition and treatment of local or distant recurrence
can prolong survival
Two thirds of recurrences develop within two years of initial surgery
Close surveillance, including regular history and clinical examination +
periodic imaging (US or MRI and CXR), is important
In the UK there are varying practices and duration of follow-up
Follow up

43. Table 5 – Summary of European Society for Medical Oncology guidelines
for follow-up in STS
Follow Up
Years since diagnosis Frequency of follow-
up
High grade tumours
1-3 3-4 months
4-5 6 months
More than 5 Annually
Low grade tumours
3-5 4-6 months
More than 5 Annually

44. Soft tissue lumps are common, but STS account for only 1% of adult
cancers
Distinguishing between malignant and benign lumps is difficult but
important because early diagnosis improves outcomes
A lump that is deep to fascia, increasing in size and/or painful and >5cm
warrants urgent referral
Treatment options include wide surgical excision alone, excision with
pre/post operative radiotherapy and adjuvant chemotherapy
Newer techniques of limb salvage surgery and adjuvant radiotherapy have
reduced the need for amputation
summary

45. 1.Sinha S, Peach AHS. Diagnosis and Management of soft tissue sarcoma. BMJ 2010; 341: c7170
2.Rydholm A. Improving the management of soft tissue sarcoma. BMJ 1998; 317: 93-93
3.Canter RJ et al. Interaction of histologic subtype and histological grade in predicting survival for soft
tissue sarcomas. J Am Coll Surg 2010; 210:191-8
4.Wibmer C et al. Increasing incidence rates of soft tissue sarcomas? A population-based epidemiologic
study and literature review. Ann Oncol 2010; 21:1106-11
5.Cormier, JN, Pollock, RE. Soft Tissue Sarcomas. CA: A Cancer Journal for Clinicians 2004; 54 (2):
94–109
6.Bali A et al. Malignant Fibrous Histiocytoma - An Unusual Transformation from Benign to Malignant. J
Cancer Sci Ther 2010;2: 053-057
7.Rekhi B, Navale P, Jambhekar N A. Critical histopathological analysis of 25 dedifferentiated
liposarcomas, including uncommon variants, reviewed at a Tertiary Cancer Referral Center. Indian J
Pathol Microbiol 2012;55:294-302
8.Lawrence W et al. Adult soft tissue sarcomas: A pattern of care survey of the American College of
Surgeons. Ann Surg 1987; 205:349-59
9.National Institute for Health and Clinical Excellence. Improving outcomes for people with sarcoma. The
manual. NICE 2006
10.Grimer R et al. Guidelines for the management of soft tissue sarcomas. Sarcoma 2010; 506182;
online
References