SKIN AND SOFT TISSUE 1 | DRA. MA.
SALOME FERNANDEZ | FEBRUARY 22, 2022
SOFT TISSUE SARCOMAS
OVERVIEW
• HETEROGENOUS group of tumors that arise from:
1. EMBRYONIC MESODERM - predominantly
2. ECTODERM as PNS
• Majority occurs spontaneously
• Germline mutations
CAUSES
• Radiation
• Environmental Exposure
• Extremity (50-60%) - most
common primary site
• Trunk (19%)
• Retroperitoneum (15%)
• Head and Neck (9%)
SITES
The anatomic site of primary
sarcoma influences treatment and
outcome - there is different
management for extremities
sarcomas, retorperitoneal and
abdominal sarcomas
Historically, the most common subtypes in adults (excluding Kaposi’s
sarcoma) were:
• Malignant fibrous histiocytoma (28%
• Liposarcoma (15%)
• Leiomyosarcoma (12%)
• Synovial sarcoma (10%)
• Malignant peripheral nerve sheath tumor (6%)
now classified as either leiomyosarcoma,
pleomorphic undifferentiated sarcoma,
Malignant fibrous
myxofibrosarcoma, or dedifferentiated
histiocytoma (28%)
liposarcoma based on cellular differentiation
and genetics
• the most common soft tissue sarcomas of
Embryonal/alveolar
childhood
rhabdomyosarcomas
Pleomorphic • occurs predominantly in adults which has a
rhabdomyosarcoma different
Pediatric Sarcomas are usually classified into
• Rhadbomyosarcoma
• Non-rhabdo myosarcoma
A lot of tumors in pediatric age group os rhabdo
There’s a type (pleomorphic) that occurs in adult but different
management
RISK FACTORS
• Multimodality approach has been applied for the
past 25 years
• Led to some improvements In survival, local control,
and quality of life
Extremity
• Before when patients have extremities sarcoma,
Sarcomas
doctor’s would offer patients to undergo amputation
• Now there’s limb sparing procedure that allows
sarcoma to be removed without undergoing
amputation
Abdominal • Continue to have high rates of recurrence and poor
Sarcomas overall survival
• 50-60% for all stages of sarcoma - which means that
Overall 5-year
in 5 years time 50% of patients would have died
survival rate
(aggressive)
• Cause of death of most patients with Soft Tissue
Lung Sarcomas
Metastasis • 80% of the time occurs within 2-3 years of initial
diagnosis
Take not that even if patients received definitive surgery, curative
resection, sarcomas have high rate of recurrence so be keen in looking
for it. Because recurrence can be as aggressive as the primary tumor
• Rare but well-stablished risk factor for STS
Radiation-induced mutations of the p53 gene
• An 8-fold to 50-fold increase in the incidence of
sarcoma among patients treated for cancer of the
breast, cervix, ovary, testes, and the lymphatic
system
Radiation
• Effects are dose-dependent and they typically occur
at the periphery of the radiation field
• Median latency period (exposure to development):
10 years
• Postirradiation sarcomas usually diagnosed at
advanced stages and generally have poor prognosis
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 • Herbicides such as phenoxyacetic acid • LI-FRAUMENI SYNDROME (LFS)
• Wood preservatives containing CHLOROPHENOLS - Extremely rare
• “VAT OF CHEMICALS OF HEPATIC ANGIOSARCOMA” - Autosomal dominant
- Vinyl - A hereditary cancer predisposition syndrome
- Arsenic - This means that a person who has LFS will
- Thorotrast have an increased risk of developing cancer

PATHOPHYSIOLOGY OF SARCOMAS

• Sarcomas are tumors of the connective tissue, and thus the tumors
may occur in bone, cartilage, fat, muscle or vascular or
hematopoietic tissues
• Common form of plastic (PVC - • Rare compared to carcinomas
Chemical Vinyl
polyvinyl chloride) • Tend to grow locally and invade adjacent tissues
Exposure Chloride
• Prolonged exposure

• Pharmaceutical, wood preservatives, CLINICAL PRESENTATION

agricultural chemicals, and
Arsenic applications in the mining,
metallurgical, glass-making, and
semiconductor industries
• Thorium oxide
• Thorium-based IV contrast dye
1930-1955
Thorothrast
• Patients diagnosed with hepatic
angiosarcoma ~ 20 to 30 year post-
exposure
• STEWART-TREVES SYNDROME
- Development of LYMPHANGIOSARCOMA after
Axillary Lymph Node Dissection and those
underwent MRM
Chronic - Has also been reported occurring in lower
Lymphedema extremities of patients with
A. Filarial infection in lower extremities
(elephantiasis)
B. Congenital lymphedema
C. Heritable lymphedema
• NEUROFIBROMATOSIS-1 / VON RECKLINAHUSEM’S
DISEASE
- Autosomal dominant condition caused by
mutations of NF 1 tumor suppressor gene on
Chromosome 17
- ~ 3-15% additional risk of malignant disease
including malignant peripheral nerve sheath
tumor (MPNST) and (GIST)
• Asymptomatic mass - most common presentation
- Usually patient is a late stage, because they won’t consult unless
they feel anything
• Deep Vein Thrombosis (DVT)
• Patients may present with complaints of hard mass or a pain when
there is pressure on the nearby nerves and soft tissues
• Tumors in the distal extremities are generally smaller, whereas tumors
in proximal extremities and retroperitoneum can grow quite large
before becoming apparent
• Obstructive GI symptoms and neurologic symptoms due to
compression of the lumbar or pelvic nerves
EVALUATION
• Radiation exposure
History • Exposure to risk factors
• Times mass has been there, changes in size, etc.
• Look for café au lait spots
• Feel the LN basins for enlargement
Physical Exam
• Evaluate neurovascular deficits with lower extremity
lesions
• Very important in management for all patients with
sarcomas. Obtain good imaging
• Defines the local extent of the tumor
• STAGES malignant disease
• Assists in PERCUTANEOUS BIOPSY - for deep-seated
sarcomas and not palpable but seen in imaging
• Aids in the DIAGNOSIS of soft tissue tumors
Imaging
POINTS TO CONSIDER REGARDING IMAGING AND BIOSY
1. Extent of mass on PE
2. Neurovascular involvement
3. Nodal involvement or distant metastasis
4. Resectability
5. Potential postoperative functional disabilities

To assess for lung metastases in patients with

CHEST CT
high-grade tumors >5 cm
Germline
Mutations CHEST X-RAY Sufficient for small or low-grade lesions

Should be performed for patients with

sarcomas capable of metastasizing to the
• CAFE AU LAIT SPOTS - seen in early childhood in
abdomen and/or pelvis
patients with NF1 Germline Mutation; flat brown ABDOMINAL / PELVIC
• Myxoid round cell liposarcoma
lesions (black arrow) CT
• Leiomyosarcomas
• As child grow older neurofibromas start appearing
• Epithelioid sarcomas
(white arrow)
• Angiosarcomas
Other familail conditions:
Has been advocated for
a. Hereditary Retinoblastoma TOTAL SPINE MRI
MYXOID ROUND CELL LIPOSARCOMA
b. Li-Fraumeni Syndrome
c. GARDNER SYNDROME
• Considered for patients
- Results from defect in the APC gene
• with ALVEOLAR SOFT PART sarcomas and
(Adenomatous polypsis coli tumor suppressor MRI OF THE BRAIN
ANGIOSARCOMAS which can metastasize to
gene)
the brain
- Increased risk of developing intraabdomianl /
mesenteric desmoid tumors

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 • For patients who cannot undergo MRI ROLE OF MRI:
(Magnetically activated implanted devices 1) Assess tumor recurrence after surgery
which 2) BASELINE IMAGE is usually obtained 3 months after the surgery
may be de-programmed): • Some clinicians believe routine post-op imaging of primary tumor site
• Cardiac pacemakers is NOT necessary for asymptomatic patients
• Insulin pumps • Difficult to detect early recurrence in scarred irradiated tissue
ULTRASOUND • Neurostimulators • Others advocate routine imaging every 6 months for the first 2 years
• Cochlear implants
• Useful adjunct to MRI when findings are
DIAGNOSIS
• Indeterminate and for delineating adjacent
vascular structures TYPES OF BIOPSIES:
• For postoperative surveillance
• To guide biopsies 1) Fine Needle Aspiration (FNA)
2) Core Needle Biopsy
BIOPSY 3) Open / Surgical Biopsies
• Preferred imaging for evaluating
• retroperitoneal, intra-abdominal, and truncal A) Incisional Biopsy
sarcomas B) Excisional Biospy

RETROPERITONEAL SARCOMAS
• preferred imaging • CT guidance can enhance the positive yield by
• Provides detailed survey of abdomen and pelvis more accurately pinpointing the location of a
• Can delineate adjacent organs and vascular tumor
structures CORE NEEDLE
• Precise localization of the tumor is important to
BIOPSY
avoid sampling necrotic or cystic areas of the
tumor (Pathologists need viable samples)
• CT-guided CNB has an accuracy rate of 93%

COMPUTED
TOMOGRAPHY (CT)

EXREMITY SARCOMAS

• CT useful if MRI is not available or cannot be

used
• For MYXOID LIPOSARCOMA:
CT of abdomen and pelvis should be done
• Safe, accurate, and economical procedure for diagnosing sarcomas
Known to metastasize to the abdomen
• Local anesthesia is given during this procedure
• Hollow needle is used to withdraw small cylinders (or cores) of tissue
BOTH ULTRASOUND AND CT CAN ASSIST IN
from the lesion
GUIDING FNA and CORE Biopsy at INITIAL
• G14, 16, 18 - US-CNB performed with small needles (16 and
DIAGNOSIS AND AT RECURRENCE
• 18 gauge) had the same diagnostic accuracy as that performed with
14-gauge needles, regardless of the lesion characteristics [the smaller
• Favored for STS of extremities
number, bigger the size]
• Most useful imaging for extremity sarcomas
because of:
MRI (MAGNETIC ✓ SOFT TISSUE contrast resolution •When core biopsy is not adequate
RESONANCE ✓ MULTIPLANAR capabilities •Allows adequate tissue for HISTOLOGIC
IMAGING) ✓ Accurately delineates MUSCLE GROUPS and IDENTIFICATION of bone or soft tissue sarcomas

distinguishes among bone, vascular - SMALL TUMORS (<3 cm); Excisional Biopsy
structures, and tumor
can be performed
- DEEP & LARGE TUMORS; Incisional Biopsy is
OPEN BIOPSY indicated; incisional removes the entire
mass
•IDEALLY should be done by the surgeon who will
perform the definitive surgery
• Incision should be oriented LONGITUDINALLY
along the extremity - to allow subsequent wide
local excision that encompasses biopsy site,
scar, and tumor en bloc

Sagittal and Coronal views allow evaluation of anatomic compartments

in 3D

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 •Because in formal resection, site of biopsy is
included
•Planning starts from the biopsy
• POORLY-ORIENTED BIOPSY incision will cause:
✓Large surgical defect for a WLE
✓Larger postoperative radiotherapy field to
encompass all tissues at risk
•ADEQUATE HEMOSTASIS should be achieved at
OPEN BIOPSY
the time of biopsy to prevent dissemination of
tumor cells into adjacent tissue planes by
hematoma
From Schwartz: an open surgical biopsy was the
gold standard for achieving adequate tissue for
definitive and specific histologic diagnosis of bone
or soft tissue sarcomas.
FEATURES:
•Lower diagnostic accuracy rate (60–90%)
than CNB
•Often NOT sufficient for establishing a
specific histologic diagnosis and grade
FINE NEEDLE ASPIRATION •Procedure of choice to confirm or rule
(FNB) out the presence of a metastatic focus or
local recurrence
•DEEP TUMORS may require an
interventional radiologist to perform the
technique under Ultrasound or CT
•If skills not present, surgeon may do it

INCISIONAL BIOPSY

ROLE: • Fine needle is done with local anesthesia

• Has an extra space - when aspirating, you get higher vacuum
• When core needle
biopsy cannot produce • When doing FNB and no special device, a 10cc syringe with G21
adequate tissue for needle
diagnosis
• When findings on core
needle biopsy are GRADING
nondiagnostic
• A unique aspect of sarcoma staging is theinclusion of TUMOR GRADE,
which is one of the most important prognostic factors

DISADVANATAGES:
• Need to schedule the
procedure
• Need for general
anesthesia
• High costs
• If inappropriately placed
can result to more
extensive definitive
resection to incorporate
the biopsy incision
• Complication rates ~ to
17%
POTENTIAL COMPLICATIONS:
• Hematoma
• Infection
• Wound dehiscence
• Tumor fungation
From Schwartz: Incisional biopsy should
be performed only by surgeons
experienced in the management of soft
tissue sarcoma, ideally in a center
specializing in the treatment of sarcoma
and by the surgeon who will perform
the definitive surgery
• 7th edition of the AJCC staging system for soft tissue sarcomas is
based on:
✓ Histologic grade of aggressiveness
✓ Tumor size and depth
✓ Presence of nodal or distant metastases
• This system DOES NOT apply to:
1. GIST
2. Fibromatosis (desmoid tumor)
3. Kaposi’s sarcoma
4. Infantile fibrosarcoma

EXCISIONAL BIOPSY

• Can be performed for easily

accessible (superficial) extremity or
truncal lesions < 3 cm.
• Should not be performed for lesions
involving the hands and feet
because such biopsies may
complicate definitive reexcision.
• For sarcomas confirmed excisional
biopsy - Microscope residual
disease jas been reported in up to
695 of reexcision specimens
• When margins are (+) or uncertain -
rate of local recurrence is 30%-40%
reexcision is NOT done

• When done for DIAGNOSIS

- Margin status is often not
• Wide en bloc excision / resection / adequately evaluated on
wide local excision (WLE) pathology exam
- tumor excision with a rim of • If detailed description of
normal tissue surgical procedure and the
- Seldom performed as a pathology specimen are not • Staging system for STS is an extension of the TNM system that includes
diagnostic procedure provided, the margins should G for histologic grade
be classified as UNCERTAIN / Staging Criteria relies on:
UNKNOWN 1. Histologic Grade
2. Tumor size and Depth
UNCERTAIN / UNKNOWN MARGIN - this classification is associated with 3. Presence of Nodal Disease
the same prognosis of reaction margins that are positive for tumor cells 4. Presence of Distant Metastases

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 • Most important prognostic factor for patients with
STS

FOR ACCURATE DETERMINATION OF GRADE

✓ Adequate tissue sample must be appropriately
fixed, stained, and reviewed by and experienced
sarcoma pathologist

FEATURES THAT DEFINE GRADE:

a) Cellularity
b) Differentiation - Good, Moderate, Poor /
Anaplastic
c) Pleomorphism
d) Necrosis - Absent, <50% or ≥50%
e) Number of mitosis per high-power field - <10,
10-19, or ≥20

• Tumor grade has been shown to predict metastasis

and overall survival
HISTOLOGIC
GRADE METASTATIC RATE BASED ON GRADE

Low-grade 5-10%

Intermediate Grade 25-30%

High-grade 50-60%

3-TIER TUMOR GRADES Following the recommendation

of the College of American Pathologists

GRADE 1 Well-differentiated

GRADE 2 Moderately differentiated

GRADE 3 Poorly differentiated

TUMOR AGGRESSIVENESS / METASTATIC POTENTIAL

GARDE 1 Considered low-grade

GRADES 2 7 3 Considered high-grade

CLASSICAL (OLD) STRATIFICATION ON THE BASIS OF

SIZE

T1 lesions ≤ 5cm

T2 lesions >5 m

AJCC CANCER STAGING HANDBOOK

(8th ed)-SUBSITES have been created:
• Head and neck
• Extremity and trunk
• GIT
• GUT
• Viscera and peritoneum
• Gynecological sites
TUMOR SIZE & • Breast lung, pleura and mediastinum
LOCATION • Other histology

HEAD and NECK SARCOMAS:

- Size criteria been reduced from the classic
criteria because of a worse prognosis at smaller
sizes

TRUNK and EXTREMITY SARCOMAS:

- Reclassified relative to size criteria for tumor
stage, changing the categories:

T1 lesion <5cm

T2 tumors 5 - 10cm

T3 tumors 10 -15cm

T4 tumors > 15cm

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 Lymph Node arising from STS are rare TREATMENT

Higher incidence of nodal involvement for: • GOALS - maximize the likelihood of long-term recurrence-free survival,
• Epithelioid sarcoma while minimizing morbidity and maximizing function
• Pediatric rhabdomyosarcoma
• Clear cell sarcoma
• Synovial sarcoma
• Myxofibrosarcoma
• Angiosarcoma

7th edition of the AJCC staging system:

• Sarcoma with nodal metastases was reclassified as
stage III rather than stage IV
- Because studies reported better survival for
NODAL
patients with isolated regional lymph node
METASTASIS
metastases treated with radical
lymphadenectomy than for patients with distant
metastases

8th edition of the AJCC, nodal disease has been

revisited
• N1 disease behaves similarly between stages III and
IV and is now captured as stage IV

SUSPICIOUS regional LNs (clinically or

radiologically):
• LN metastases should be confirmed or ruled out by
either fine-needle aspiration or core biopsy before
radical lymphadenectomy
• Wide local excision
• Occur most often in the LUNGS • Amputation
• Selected patients with pulmonary metastases may Surgery
• Isolated regional perfusion
survive for long periods after surgical resection and • For local control
chemotherapy

DISTANT
Radiation Therapy - for local control)
METASTASIS
Other potential sites of metastasis include:
• Bone • Adjuvant chemotherapy
• Brain Systemic Therapy • Neoadjuvant / Preoperative chemotherapy
• Liver • For systemic control
• Visceral and retroperitoneal sarcomas have a
higher incidence of liver and peritoneal metastases PRIMARY TUMORS

• If with no evidence of distant metastasis → Managed with SURGERY

PROGNOSTIC FACTORS only
• When wide pathologic margins cannot be achieved because of
1. Primary Tumor Size anatomic constraints and/or HIGH-GRADE tumor → SURGERY +
2. Grade RADIATION THERAPY
3. Depth
- All of which are incorporated into the staging system] • Tumor location
4. Histology • Tumor size
5. Tumor Site Type of Surgical • Depth of invasion
6. Presentation (local recurrence or initial diagnosis) Resection • Involvement of nearby
7. Patient factors - such as older age and gender has also been determined by the • structures
associated with recurrence and morality following factors • Need for skin grafting or autogenous tissue
8. Positive microscopic margins & early recurrence after resection of reconstruction
an extremity sarcoma have been shown to be associated with • Patient’s performance status
decreased survival
9. Ki-67 - proliferation marker; correlated with a poor clinical outcome For HIGH-GRADE Limb-sparing surgery - recommended (National
in high-grade extremity sarcomas extremity sarcomas Institutee of Health, 1985)
10. E-cadherin and catenins - proteins essential for intercellular junction;
associated with poor outcome in patients with STS For primary or AMPUTATION - treatment of choice
11. Higher CD100 expression - correlate with higher proliferative recurrent tumors that
potential and poor outcome cannot be grossly
resected with a
limb-sparing
procedure and
preservation of
function (<5% of
atients)

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 SURGERY
GOAL
To achieve a complete resection (not leaving any tumor behind R0)
Reason: Microscopically (+) of Grossly (+) resection margins are
associated with increased risk of recurrence and death
• If unexpected POSITIVE margin is found on pathologic examination of
the resection specimen → RE-EXCISION should be performed if
feasible
• RATIONALE:
• (+) margin, especially in macroscopic residual disease
• Local control is unlikely even with the addition of postoperative RT
(Shows importance of a well-planned initial operation)
Preferred treatment for
extremity sarcomas which
includes resection of the
BIOPSY SITE
GOAL
1. To remove the tumor with
approximately 1 to 2 cm of
WIDE LOCAL EXCISION
surrounding normal soft tissue
2. Narrower margins may be necessary
to preserve uninvolved critical
neurovascular structures and may
be adequate for patients
undergoing radiation therapy
3. Dissection should proceed through
grossly normal tissue planes not
abutting the tumor
• Although associated with increased rates of post- operative
complications, showed encouraging results
•Local recurrence and 5-year survival rates are similar to those patients
not requiring vessel resection for their tumors
•Studies have also shown acceptable functional outcomes with
resection of the sciatic, tibial, and peroneal nerves with appropriate
reconstruction and rehabilitation
BONE INVASION (if there’s bone
deformity) for extremity STS
•Can be identified using MRI
•Occur in about 5% of patients
and is associated with reduced
overall survival → bone
resection is required to obtain
an adequate surgical margin
and to achieve local control
Lin et al: In absence of frank
cortical bone penetration:
•PERIOSTEUM is an adequate
surgical margin for sarcomas
treated with wide excision and
radiation
STS of DISTAL EXTREMITIES
(Hands/ Feet)
• Technical challenge
• Often detected at a smaller size
(<5 cm) than proximal-
extremity tumors
• But resection and
reconstruction techniques are
often more complex
• Preoperative planning is critical
to obtain favorable functional
outcomes
✓MRI is essential to identify the
proximity of the tumor to
underlying critical structures
(e.g., bone, tendon, or
neurovascular structures)

For LOCALLY advanced tumors:

• Repair of bone defects, vascular reconstruction, tendon transfers, and
soft tissue reconstruction using regional or free flaps have resulted in
good functional outcomes
•STS is generally surrounded by a thin layer of fibrous tissue known as the
PSEUDOCAPSULE • Amputation remains a
❖ Pseudocapsule should not be used to guide resection reasonable option for patients
(enucleation) as microscopic disease exists within this reactive zone with soft tissue sarcomas of the
• If the tumor is adjacent to or displacing major distal extremities when
• neurovascular structures: acceptable oncologic or
✓These do not need to be resected but the adventitia or perineurium functional outcomes cannot
should be removed
✓ All patients undergoing
•For massive tumors of the extremities: resection of extremity sarcomas
✓Wide local excision entails a radical or complete anatomic should undergo physical
compartment resection therapy beginning immediately
✓Surgical clips should be placed to delineate the extent of the after surgery and continuing
resection bed for patients likely to require postoperative radiation until maximum function is
therapy achieved

• Radical en bloc resection with vascular reconstruction in the lower

extremities

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 • Improved survival was reported for patients
• Vessels are dissected, and all collateral vessels are ligated
with isolated regional LN metastasis
• Vessels are then cannulated and connected to a pump oxygenator
✓ Before this procedure is done, patients with
• A tourniquet for ESMARCH BAND is applied to the limb to achieve
clinically or radiologically suspicious
RADICAL complete vascular isolation
regional nodes should have metastases
LYMPHADENECTOMY • Chemotherapeutic agents are added to the perfusion circuit and
confirmed by biopsy → an Ultrasound-
circulate for 90 minutes
Guided FNB or CNB of lymph nodes in
• The temperature of the perfused limbs is maintained by external
selected patients with suspicious clinical or
heating and warming the perfusate to 40°C (104°F)
radiologic findings is recommended

• Remained controversial for STS despite the PURPOSE: To give the chemotherapy drug (high dose) on the limb,
recognition that several histologic subtypes of sparing the body from the toxicity
high-grade sarcoma are known to have a
propensity for lymph node metastasis
• SENTINEL LN BIOPSY • NO prospective studies of the sensitivity and
specificity for sarcomas → As such, sentinel
node biopsy for sarcoma should only be
performed in either highly selected patients or
in the setting of a clinical trial

• Historically, RADIAL RESECTION / AMPUTATION

was standard for treatment of STS

REASON: Local excision of STS has resulted in

local failure rates of 50-70%, even when a
margin of normal tissue around the
tumor was excised
• Today, the addition of RADIATION THERAPY to
less radical surgical resection has made limb
salvage possible in most cases

• AMPUTATION versus LIMB- SPARING SURGERY • Over the next 20 years, isolated perfusion of extremity to treat
followed by adjuvant radiation therapy sarcoma fell out of favor
performed by the National Cancer Institute • Improved survival and decreased local recurrence rates could be
between 1975 and 1981 → NO significant obtained with LESS RADICAL THERAPY
AMPUTATION
difference between the two groups in local • Although to date the technique has been well established for patients
recurrence or overall survival rate with locally advanced extremity disease for melanoma, its application
• Potter and colleagues later reviewed the for advanced, locally recurrent extremity sarcoma deserves further
entire National Cancer Institute experience study
with 123 patients treated with conservative
surgery plus radiation therapy and 83 treated RADIATION THERAPY
with amputation → Local recurrence rate was
significantly higher in the surgery and INTERMEDIATE- or HIGH- Standard treatment guidelines required RT
adjuvant radiation therapy group: 8% versus grade tumors of any size after surgery
0% in the amputation group
✓ SURVIVAL RATES did not differ between the • Have not generally been associated with
groups SMALL tumors (≤5 cm) local recurrence
• Several large single-institution studies have • RT for such tumors may not be necessary
also reported favorable local control rates
with conservative resection plus RT A. External-beam RT - can be delivered
using photons or particle beams
• Limb-sparing technique MODES of Radiation (electrons, protons, pions, or neutrons)
• STS is perfused with high concentrations of Therapy B. Brachytherapy
tumor necrosis factor- alpha (TNF-α) and C. Intensity-modulated RT [IMRT]
melphalan under hyperthermic conditions →
The use of TNF-α is not approved by the U.S.
Food and Drug Administration (FDA) and is • The optimal MODE and TIMING of radiation therapy (preoperative,
used only in European countries intraoperative, or postoperative) have yet to be defined
• Conventional fractionation is usually 1.8 to 2 Gy per day
Generally used for:
- Locally advanced ✓CT SCAN is needed if patient is undergoing RT
- Multifocal - Integral part of RT
- Locally recurrent disease - Can define gross tumor volume
ISOLATED
- Estimate margin of tissue at risk of microscopic tumor involvement
REGIONAL
• It has also served as a PALLIATIVE treatment to
PERFUSION
achieve local control for patients with distant • Standard margin: 5- 7 cm
metastases Optimal radiation margin
• o Some centers advocate wider margins
• MAIN ARTERY and VEIN of the perfused limb is is NOT well defined:
for tumors larger than 15 cm
isolated from the systemic circulation
• 50 Gy given in 25 fractions
THE CHOICE OF ANATOMIC APPROACH IS • Resection is performed 4 to 8 weeks after
Typical PREOPERATIVE
DETERMINED BY THE TUMOR SITE completion of RT to allow acute radiation
dose:
1. External Iliac Veins - thigh tumors changes to subside
2. Femoral or Popliteal Vessel - calf
tumors A. Tumor site
POSTOPERATIVE radiation
3. Axillary Vessels - upper extremity B. Surgical margins
therapy PLAN is based
tumors C. Tumor grade
on:
D. Institutional preferences

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 TOXIC EFFECTS OF Local toxic effects of radiation therapy vary
• Metallic clips are placed in tumor bed during surgery can help define RADIATION according to radiation dose, field size, and timing
the limits of the resection and aid in RT planning THERAPY
• Entire surgical scar and drain sites should be included in the field so
that near-full dose can be administered to the superficial skin 1. Wound dehiscence
2. Seroma formation
POST OPERATIVE RT DOSE: 60-70 Gy 3. Wound necrosis
PREOP RT
4. Ulceration
COMPLICATIONS:
5. Infection
6. Persistent drainage
7. Cellulitis

• Seen in free flaps

• Wound complications (usually)
• Patients should be advised that secondary
POSTOPERATIVE RT surgical repair may be necessary
COMPLICATIONS: • Preoperative radiation rather than
postoperative radiation for larger tumors
requiring flap reconstruction is a logical and
sound approach

• Occur after >1 year of completion of therapy

1. Fibrosis/ contracture
• Placement of multiple radioactive seeds LONG-TERM 2. Lymphedema
through catheters inserted in the tumor CHRONIC EFFECTS: 3. Neurologic injury
resection bed 4. Osteitis
• Afterloading catheters are placed 5. Fracture
• in 1-cm increments while leaving a 2- cm
BRACHYTHERAPY margin around the surgical bed 1. Larger tumors
• After adequate wound healing is confirmed, 2. Higher doses of radiation (>63 Gy)
usually after the 5th postoperative day, the POORER functional 3. Longer radiation fields (>35 cm)
catheters are loaded with seeds containing outcome after RT: 4. Poor radiation technique
iridium-192 that deliver 42 to 45 Gy of radiation 5. Neural sacrifice
to the tumor bed over 4 to 6 days 6. Post-operative fractures
7. Wound complications
• Shorter overall treatment time
of 4 to 6 days, compared to
the 4 to 6 weeks generally SYSTEMIC THERAPY (CHEMOTHERAPY)
required for preoperative or
postoperative RT (primary 1) For patients considered at HIGH RISk of death from sarcoma
ADVANTAGES
advantage) ✓ Those presenting with metastatic disease
• Lower cost comparing ✓ Localized sarcomas at non-extremity sites
adjuvant brachytherapy ✓ Sarcomas of intermediate- or high-grade histology larger than 5 cm
versus adjuvant external- 2) For most patients with sarcoma, results of conventional
beam irradiation for chemotherapy regimens have been poor
3) Chemosensitivity of soft tissue sarcoma varies by HISTOLOGIC
• Requires significant expertise, subtype, but there are some subtype that responds to chemotherapy
PRIMARY
extended inpatient stay and
DISADVANTAGE •Synovial Sarcoma
bed rest
CHEMOSENSITIVE
•Myxoid / Round Cell Liposarcoma
TUMORS
•Uterine leiomyosarcoma

• Pleomorphic liposarcoma
• Myxofibrosarcoma
• Epitheloid sarcoma
INTERMEDIATE
• Leiomyosarcoma
SENSITIVE
• Malignant Peripheral Nerve Sheath Tumor
TUMORS
(MPNSTs)
• Angiosarcoma
• Desmoplastic round cell tumore

• Clear cell sarxoma

RELATIVELY • Endometrial stromal sarcoma
CHEMORESISTANT • Alveolar soft part sarcoma
• Delivers radiation more precisely to the tumor • Extraskeleta myxoid chondrosarcoma
than external-beam irradiation while minimizing
INTENSITY- the volume of surrounding tissues exposed to
MODULATED RT high radiation
(IMRT)
1. Less risk of postoperative
wound infections because
of minimized dose to the
skin
2. Protection of underlying
bone (e.g., femur) as a
Proposed
result of concave dose
benefits of
distributions
preoperative
3. Sophisticated computer
IMRT:
planning algorithms are
used to deliver radiation
doses to the tumor in 3
DIMENSIONS while limiting
doses to radiation sensitive
organs monami 9 of 16
 Most active chemotherapy
agents in metastatic STS
DOXORUBICIN
• first line treatment for
advanced disease
• 75mg/m2 every 3 weeks
• Treatment duration is based
on response, but a maximum
of 6 cycles is generally
recommended because of
DOXORUBICIN the risk of cumulative
& IFOSFAMIDE cardiotoxicity
IFOSFAMIDE
• Recommended 2nd-line
treatment
• Recommended for 1st-line
treatment in patients with
STANDARD cardiac morbidity
CHEMOTHERAPY • Standard Dose: 9- 10 g/m2
• Synovial sarcomas have
been shown to be particularly
sensitive to ifosfamide
• As a single agent was
reported to produce
responses in 18% of patients
with advanced sarcoma
GEMCITABINE • Combined with docetaxel
has been reported to
produce response rates as
high as 53% in patients with
uterine leiomyosarcoma
Have been found to be active
TAXANES against ANGIOSARCOMAS,
(Docetaxel & particularly of the face and
Paclitaxel) scalp, likely because of their
potent antiangiogenic effects
• Doxorubicin derivative that
serves as a prodrug of
doxorubicin
• Covalently binds to
albumin in the blood until
reaching the acidic tumor
environment releasing
doxorubicin into the tissue
• Single-agent therapy
ALDOXORUBICINE showed superior efficacy
over doxorubicin:
- Prolongs progression-
free
- survival
- Improves rates of 6-
month progression-free
survival and tumor
response, warranting
further study
NOVEL
CHEMOTHERAPY • ๏Marine-derived alkaloid
that
• binds DNA, affecting
transcription and inducing
the formation of DNA
double-strand breaks
• Has shown benefit in the
treatment of advanced
soft tissue sarcomas,
particularly
TRABECTEDIN
leiomyosarcoma, myxoid
liposarcoma, and other
translocation related
sarcomas
• Generally well-tolerated
but is associated with
prolonged and severe
neutropenia,
thrombocytopenia, and
hepatic toxic effects
SURVEILLANCE
• Most useful components of follow-up in
HISTORY AND PE • evaluating LOCAL RECURRENCE after
• definitive treatment
• Useful for evaluating less accessible
regions,
CT & MRI • such as the retroperitoneum
• Useful in assessing EQUIVOCAL CHANGES
on examination
• Most recurrences of STS occur in the first 2
YEARS after completion of therapy
• The National Comprehensive Cancer
Network (NCCN) recommendation for
2-3 years after completion of treatment:
✓ History and physical and chest CT or
xray every 3 to 6 months
FOLLOW-UP
FOLLOW-AFTER 2-5 YEARS
✓ Follow-up intervals can be lengthened
to every 6 months
✓ Yearly imaging
FOLLOW-UP AFTER 5 YEARS
✓ Yearly evaluation and CXR
• Up to 20% of patients with extremity
sarcomas develop LOCALLY RECURRENT
DISEASE, which is often accompanied by
distant metastases
✓ ALL patients with recurrent extremity
sarcoma should undergo a FULL
STAGING assessment
• Microscopically positive margins are at
increased risk
• Median interval to local recurrence: 16
months
• INCIDENCE:
• 65% developed local recurrence by 2
RECURRENT SARCOMA years
• 90% by 4 years
TREATMENT FOR RECURRENCE OF EXTREMITY
SARCOMAS
• AMPUTATION is frequently required to
achieve negative margins
• Function-preserving resection +
additional RT, with or without
chemotherapy, can produce
acceptable rates of local control
• Primary determinant of survival in STS is
development of distant metastases
The most common initial metastasis of STS is
the LUNG
PULMONARY RESECTION will benefit the
following patients:
✓ Those with limited number of
pulmonary nodules (<4)
METASTATIC SARCOMA
✓ Those with long disease-free intervals
✓ Those with no endobronchial invasion
• For patients who are surgical candidates,
pulmonary resection alone can be more
cost-effective than watchful waiting,
chemotherapy, or chemotherapy +
surgery
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 MALIGNANT MELANOMA FEATURES OF MALIGNANT MELANOMA

ANATOMY OF THE SKIN • Arises from melanocytic cells

• Primarily involves the skin
• SKIN is made up of tissues derived from both the ectodermal and • Can also arise from: Eye (uvea, conjunctiva and ciliary body),
mesodermal germ cell layers Meninges Mucosal surfaces
• Metastasizes quite often, and can travel to most other tissues in the
• 3 distinct TISSUE LAYERS comprise the skin: body
- They differ in composition based on location, age, sex, and • This metastasis confers a poor prognosis in patients - median life span
ethnicity, among other variables: of 6 to 8 months after diagnosis
1. EPIDERMIS
2. DERMIS
3. HYPODERMIS/ SUBCUTANEOUS TISSUE PATHOPHYSIOLOGY

• Cells within the STRATUM BASALE

• Responsible for production of the pigment MELANIN in the
skin
• Derived from the NEURAL CREST

DENSITY:
~ 4-10 keratinocytes per melanocytes
~ 500 to 2000 melanocytes per mm2 of
cutaneous tissue
This density varies based on location in the body,
but differences in skin pigmentation are based on
the activity of individual melanocytes and not the
number of melanocytes

PIGMENTATION
• In darker-skinned ethnicities, melanocytes create and store
melanosomes in keratinocytes at a higher rate, but still
have a pale-staining cytoplasm on light microscopy

• Melanocytes interact with keratinocytes of the stratum

• Outermost layer basale and spinosum via long cytoplasmic extensions
• Characterized by a protective highly keratinized leading to invaginations in several keratinocytes
layer of skin
EPIDERMIS MELANOCYTES
• Stratified • TYROSINASE is created and distributed into
• 4-5 histologically distinct layers depending on the • melanosomes
• Melanosomes travel along the dendritic processes to
location in the body
eventually become phagocytized by keratinocytes and
distributed in a supranuclear orientation.
• This umbrella-like cap then serves to protect the nuclear
material from damage by radiation

• Made up of organized collagen network to

support the numerous epidermal appendages,
DERMIS
neurovascular structures, and supportive cells
within the skin

• Fatty layer below the dermis

HYPODERMIS • Functions in body processes of thermoregulation
and energy storage, among others

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1. Usually starts as benign mole BENIGN NEVUS which is produced by RISK FACTORS
controlled proliferation of normal melanocytes
2. DYSPLASTIC NEVUS • Intermittent childhood sunburns
• Abnormal growth of melanocytes in a pre-existing nevus or new • >10 tanning bed sessions (2x increased risk among
location resulting in a pre-malignant lesion with random cytologic young adults)
UV RADIATION
atypia. • Residence at high altitudes or in close proximity to
• Flat macules, > 5mm in size, with irregular borders and variable the equator
pigmentation • PUVA therapy (prolonged psoralen + UV A)
3. RADIAL GROWTH PHASE
• Natural furocoumarin
• Melanocytes acquire ability to proliferate horizontally in the • Used for their photosensitizing activity in ththerapy of psoriasis
epidermis PSORALEN and vitiligo
• Histology shows continuous atypia (melanoma in situ) • Actively taken up by epidermal cells and intercalates into
DNA
• E-cadherin helps confine the cells intraepidermally but a few cells
may invade the papillary dermis
Two types of UV light are proven to contribute to the riskfor skin
4. VERTICAL GROWTH PHASE cancer: UVA & UVB
Biochemical events:
• Loss of E-cadherin (tumor suppressor) Ultraviolet A has a longer wavelength, and is
• Expression of N-cadherin (mediates aggregation among (UVA) associated with skin aging.
melanoma cells, heterotypic adhesion of melanoma cells to
dermal fibroblasts and vascular endothelial cells, which may Ultraviolet B has a shorter wavelength and is
improve their ability to migrate through stroma and enter the UV RAYS (UVB) associated with skin burning
vasculature)
• Malignant cells invade basement membrane and proliferate • MOST dangerous type of ultraviolet
vertically in the dermis as an expanding nodule with metastatic light but cannot penetrate earth's
Ultraviolet C
potential (UVC)
protective ozone layer
5. METASTATIC MELANOMA • Poses no threat to human, animal or
• Malignant melanocytes spread to other areas of body plant life on earth
• Usually first to lymph nodes then to skin, subcutaneous soft tissue,
lungs and the brain • Dysplastic nevi (6-10% overall lifetime risk)
PERSONAL /
• Familial atypical multiple- mole melanoma syndrome
FAMILY
• Congenital nevi (risk proportional w/ size)
SUBTYPES HISTORY
- Giant congenital nevi (>20 cm)- 5-8% lifetime risk

1. Superficial spreading - most common • Fair-complexioned

2. Nodule • Red or blond hair
3. Lentigo Maligna • Light eye color
4. Acral Lentiginous PHENOTYPIC • Large number (>50) of melanocytic nevi (common
TRAITS nevi)
OTHER VARIANTS: • Presence of atypical melanocytic nevi with some of
- Amelanotic melanoma the clinical features of melanoma
- Spitzoid Melanoma • Advance freckling
- Desmoplastic melanoma
- Pigment synthesizing (animal type) melanoma Used as treatment for:

PUVA • Psoriasis
UNCOMMON SITES
THERAPY • Atopic dermatitis
• Sublingual • Vitiligo
ACRAL
• Plantar / Palmar • Graft versus host disease

• Oral Cavity
POSSIBLE SCENARIOS OF MALIGNANT MELANOMA
MUSCOSAL • Nasal Cavity
• Paranasal Sinuses
• Patient presents with a skin lesion on the arm, abdomen or back that
has recently changed in size and color
GENITAL Male and Female External genetalia
• Patient presents as a referral from a dermatologist after a BIOPSY
• Uveal
EYES
• Conjunctival PHYSICAL EXAM

2x2 cm grayish-black lesions with irregular

PRIMARY LESIONS
borders and rough surface
SURVIVAL RATE
• Smaller lesions within 2cm from the primary
•Estimated 5-year survival rate for patients whose melanoma is SECONDARY LESIONS lesion
detected early: ~98% • Small pinpoint black dots around the lesion
•Survival rate falls to 62 % when the disease reaches the LYMPH NODES
•Survival rate falls to 18% when the disease spreads to DISTANT ORGANS • Lesions >2cm away from the primary in the
TERTIARY LESIONS
direction of the LN basin

DIFFERENTIAL DIAGNOSIS

BENIGN LESIONS MALIGNANT LESIONS

• Benign nevus • Basal CA

• Seborrhic keratosis • Squamous CA
• Pigmented warts

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 DIAGNOSIS

CLINICAL DIAGNOSIS HISTOPATH DIAGNOSIS

• Excision Biopsy
• Visual Analysis (ABCE Rule)
• Incision Biopsy
• Ugly Duckling Sign
• Punch Biopsy
• Dermatoscopy
• Shave Biopsy

ABCDE Rule
(VISUAL
ANALYSIS)

• A CLINICAL PREDICTION rule devised to help

clinicians and laypeople identify suspicious lesions
✓ "E" for evolution - most important clinical
criterion for the diagnosis of melanoma
✓ "Change" can be noted by the patient or
documented by comparison of serial clinical or
dermoscopic changes

• A pigmented lesions
that is too obvious
from the others given
individual ’s
“signature nevi”
• Must be considered
UGLY DUCKLING
SUSPICIOUS even if it
SIGN
does not fulfill the
ABCD criteria
• Proposed as
additional criterion in
patients with multiple
nevi

• Examination of the skin using skin surface

microscopy
• Also called ''EPILUMINOSCOPY" or
“EPILUMINISCENT” microscopy
DERMATOSCOPY • Meta-analysis Kittler et al (2002):
- Expert’s use of dermoscopy achieved an
increase in diagnostic accuracy over the
clinical diagnosis alone with a sensitivity of 89%
and a specificity of 79%

• Imaging technology
• Allows in vivo identification of cells and tissues of
the epidermis and papillary dermis with nearly
histologic resolution
• Uses a LOW-POWER LASER that emits near-infrared
light that reflects off structures in the epidermis to
create a 3D image
REFLECTANCE
CONFOCAL RESOLUTION:
MICROSCOPY • ~ 1 millimicron, comparable with standard
histology at ~30x magnification
• Melanin granules have a high refractive index,
more light is reflected back to the confocal
microscope REFLECTANCE CONFOCAL
MICROSCOPY
• Areas of higher melanin concentration will appear
as BRIGHT areas on a confocal image

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MULTISPECTRAL
IMAGING
CLINICAL STAGING

• MULTISPECTRAL IMAGING DEVICES

MelaFind, SIAScope, MoleMate Tool

• Recommended for all

suspicious lesions
EXCISIONAL BIOPSY
• Should be done with
1-3mm margins
HISTOPATH
DIAGNOSIS
For large lesions or in a
domestically or
INCISIONAL BIOPSY
anatomically challenging
area

APPROACH BRESLOW STAGING

• Establish risk factors

• BIOPSY
• STAGE the patient
• SAMPLE the Lymph Nodes
• PLAN the treatment
• DETERMINE if adjuvant treatment is needed

• No role for CXR or CT unless there is POSITIVE

regional LN disease
✓ STAGE III or higher:
✓ High risk of distant metastasis • Measurement of DEPTH of melanoma from the surface of skin down
✓ Imaging is recommended as BASELINE through to the deepest point of the tumor
ROLE OF CXV & CT STAGING • Measured in millimeters (mm) with a small ruler, called a micrometer
• Used as another staging system for melanoma
• Additional imaging that may be needed:
✓ CT of chest, abdomen, pelvis
SENTINEL LN BIOPSY
✓ Whole body PET-CT
✓ Brain MRI
• Standard STAGING procedure to evaluate regional LNs for patients
TNM CLASSIFICATION with clinically node (-) malignant melanoma
• Almost always performed at time of initial WIDE EXCISION
• Doing SLN mapping after lymphatic violation from excision can
decrease the accuracy of the test
• Can identify the 1st draining LN from the primary lesion
• (+) Detection of subclinical metastasis --> may benefit from
LYMPHADENECTOMY or adjuvant therapy
• Surgical approach to IDENTIFY and REMOVE the sentinel lymph node
to determine if the cancer has spread, and if so, how far

• In most cases, means the cancer has NOT

NEGATIVE SLNB
spread

• Means cancer was found in the lymph node

POSITIVE SNLB
✓ COMPLETE NODE DISSECTION MUST BE DONE

PREOPERATIVE
• Preoperative lymphoscintigraphy with intradermal injections of
technetium sulfur colloid to delineate lymphatic drainage

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INTRAOPERATIVE:
• Intradermal injection of 1ml of isosulfan blue/methylene blue/
lymphazurin blue near the tumor (peritumoral)
• May also use a handheld gamma counter in locating the sentinel LN
as an additional tool - if there’s multiple lymph nodes are seen when
opened

Radioactive tracer-dye combination allows SLN to be identified in 98%

of cases
✓ INCISION over LN basin of interest allows nodes to be excised and
studied by H&E stain and immunohistochemistry

Resection is twice the diameter of the

HEAD & NECK
lesion

• Split nail to biopsy

SUBLINGUAL (FINGER) • Amputate the distal phalanx
• Do elective LN dissection if >0.75 mm

SUBLINGUAL (TOE) Ray amputation

Full-thickness wedge resection twice

EAR
the diameter of the lesion

FACE, ANTERIOR SCALP, Superficial parotidectomy + modified

Anterior to EAR with (+) Radical Node Disection (RND)
SLN

• Local excision
WHO NEEDS SLNB? • Abdominaperineal Resection (APR) only if
ANAL REGION
✓ Confirmed MALIGNANT MELANOMA (>1mm depth) but with patient is incontinent or has severe pain
clinically negative LNs from invasion of sphincters
✓ EXTREMITY and TRUNCAL primaries >1mm depth
• Do complete NODE DISSECTION if SLN (+)

Lesions ≤0.75 mm thick
Lesions 0.76 - 1mm thick:
Lesions 1.2 - 3mm thick
• SLNB did not affect disease-free survival
• SLNB NOT RECOMMENDED unless there is
significant uncertainty about adequacy
of micro staging
• SLNB may be considered in the
appropriate
clinical context
✓ (+) Ulceration
✓ High mitotic rate 1/mm2
✓ (+) Lymphovascular invasion
SLNB recommended as there is
improvement in distant metastasis free
survival
FOR CLINICALLY POSITIVE LN:
• Radical LN dissection is standard therapy
with or without adjuvant therapy
INGUINAL NODE DISSECTION
• Only done if with gross disease in the
apical nodes (saphenofemoral/Cloquet’s
INNODAL DISSECTION nodes) -or-
• CT shows suspicious iliac adenopathy
• DON’T do inguinal node dissection if
✓ only MICROSCOPIC disease in
superficial nodes or nodes that are (+)
to level of aortic bifurcation:
- Unlikely to have therapeutic
benefit
- Downside of severe leg edema

SURGERY

• European consensus-based interdisciplinary guideline for diagnosis

and treatment of melanoma 2016
• The definitive surgical excision should be
• performed with safety margins preferably within
• 4-6 weeks of initial diagnosis.

• No role for CXR or CT unless there is POSITIVE

regional LN disease
✓ STAGE III or higher:
✓ High risk of distant metastasis
✓ Imaging is recommended as BASELINE
ROLE OF CXV & CT STAGING

• Additional imaging that may be needed:

✓ CT of chest, abdomen, pelvis
✓ Whole body PET-CT
✓ Brain MRI

monami 15 of 16
 ADJUVANT THERAPY

Eastern Cooperative Oncology Group (ECOG Trials)

• Disease-free survival advantage in patients
• with melanoma >4mm thickness with or without
• LN involvement if they receive HIGH-DOSE INTERFERON (IFN)

European Organization for Research and Treatment of Cancer (EORTC

Trial)
• Recurrence-free survival benefit with pegylated IFN
- IFN therapy is not well tolerated
- The pooled analysis of these 2 trials did not show improvement in
overall-survival

STAGE II Offered high-dose interferon or vaccine

melanomas
deeper than
4mm & STAGE III

• Resection assuming there is no other evidence

of disease
STAGE IV
with isolated Otherwise, may be offered:
metastasis ✓ RT and chemotherapy
✓ Newer treatment:
- Immunotherapy

• Adjuvant cytotoxic chemotherapy

• Adjuvant immunotherapy with CTLA-4 and PD-1 antibodies
(Iplimumab)

TREATMENT OF INCURABLE METASTASU|IS

GOALS
• To prolong survival
• To reduce tumor size for resultant increase in symptom free Cours

REFERENCES
• Doc Fernandez’s lecture
• Schwartz 11th edition

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