SOFT TISSUE SARCOMA

BY: NATNAEL TEMESGEN

PGY-3
PAACS, WOLITA SODDO , ETHIOPIA
INTRODUCTION
• ARISE FROM EMBRYOGENIC MESODERM

• MOST PRIMARY SOFT TISSUE SARCOMAS ORIGINATE:

• EXTREMITY (50–60%); THE NEXT MOST COMMON SITES ARE THE TRUNK (19%),
RETROPERITONEUM (15%), AND HEAD AND NECK (9%)

• ALVEOLAR/EMBRYONAL RHABDOMYOSARCOMA IS COMMON IN CHILDREN,

PLEOMORPHIC RHABDO. MORE COMMON IN ADULTS

• OVERALL 5 YEARS SURVIVAL FOR PATIENT WITH ALL STAGES – 50-60%

• COMMONEST METS TO THE LUNG, 2-3 YEARS AFTER DIAGNOSIS MOST PATIENT
SUCCUMB TO DEATH
ETIOLOGY
• RADIATION EXPOSURE-
• MUTATION IN P53
• 8-50 TIMES RISK OF DEVELOPING SARCOMA FORM GENERAL POPULATION
• ANGIOSARCOMA, LYMPHANGIOSARCOMA, PLEOMORPHIC UNDIFFERENTIATED
SARCOMA
• OCCUPATIONAL CHEMICAL EXPOSURE
• PHENOXYACETIC ACIDS, THORIUM OXIDE (THOROTRAST), VINYL CHLORIDE, AND
ARSENIC
• TRAUMA
• CHRONIC LYMPHEDEMA
• LYMPHANGIOSARCOMA HAS BEEN ESTIMATED TO OCCUR IN 0.07% OF PATIENTS
WHO UNDERGO AXILLARY NODE DISSECTION
MOLECULAR PATHOGENESIS

• TRANSLOCATION/AMPLIFICATION-ASSOCIATED SARCOMA
• EWING SARCOMA

• ONCOGENIC MUTATION
• GIST

• COMPLEX GENOMIC REARRANGEMENT

• RETINOBLASTOMA
INITIAL ASSESSMENT AND CLINICAL
PRESENTATION
• THE CLINICAL BEHAVIOR OF MOST SOFT TISSUE SARCOMAS IS DETERMINED
BY
• ANATOMIC LOCATION
• HISTOLOGIC SUBTYPE
• GRADE OF AGGRESSIVENESS
• SIZE
• MOST COMMONLY PRESENT AS ASYMPTOMATIC MASS
• OTHER PRESENTATIONS
• DVT
• PAIN, EDEMA AND SWELLING
• OBSTRUCTIVE GI DISEASES
DIAGNOSTIC MODALITY

• MRI- THE PREFERRED IMAGING TECHNIQUE

• CT-MOST USEFUL TO EVALUATE THE INTRAABDOMINAL, RETROPERITONEAL
AND TRUNCAL SARCOMA
• USEFUL TO ASSESS METS TO THE LUNGS
• ULTRASOUND- IF MRI IS INDETERMINATE AND ASSESS FOR VASCULAR
INVOLVEMENT
• FOR POST OPERATIVE SURVEILLANCE
• FOR GUIDING BIOPSY
• PET
• BIOPSY- CORE NEEDLE BIOPSY(93%)> FNAC(60-90%)
• INCISIONAL BIOPSY VS EXCISIONAL BIOPSY
STAGING AND PROGNOSTIC FACTORS(STAGING)
• COMMONLY STAGED USING THE AJCC GUIDELINE

1. HISTOLOGIC GRADE- CELLULARITY, DIFFERENTIATION, PLEOMORPHISM,

NECROSIS AND NUMBER OF MITOSIS
• PREDICTS METASTASIS AND OVERALL SURVIVAL

2. TUMOR SIZE AND LOCATION- CLASSIFICATION OF ABOVE AND BELOW FASCIA

IS NOW OBSOLETE

3. NODAL METASTASIS-IF PRESENT, CLASSIFIED AS STAGE 4

4. DISTANT METASTASIS- MOST OFTEN TO THE LUNGS, OTHER SITES ARE BONE,
BRAIN AND LIVER(MOSTLY RETROPERITONEAL SARCOMAS)
 TREATMENT OF EXTREMITY AND TRUNK
SARCOMA
• GOALS:
• MAXIMIZE LONG TERM RECURRENCE FREE
SURVIVAL
• MINIMIZING MORBIDITY
• MAXIMIZING FUNCTION

• OVER ALL SURVIVAL FOR PATIENTS WITH ALL

STAGES OF SOFT TISSUE SARCOMA IS 50-60%

• MOST PATIENT WHO DIE, DIE FROM OF

METASTATIC DISEASE WHICH BECOMES
EVIDENT WITH 2-3 YEARS OF INITIAL
DIAGNOSIS IN 80% OF CASES
SURGERY

• SURGERY ALONE VS SURGERY + RADIATION THERAPY

• AMPUTATION IS THE PROCEDURE OF CHOICE FOR EXTREMITY SARCOMA

• SURGERY SHOULD BE MARGIN NEGATIVE BOTH GROSSLY AND

MICROSCOPICALLY

• IF POSITIVE MARGIN FOUND AFTER RESECTION- RERESECTION SHOULD BE DONE

• POSITIVE MARGIN IS ASSOCIATED WITH LOCAL RECURRENCE AND DEATH

WIDE LOCAL EXCISION
• PREFERRED TT FOR EXTREMITY SARCOMA, BIOPSY SITE SHOULD BE INCLUDED

• 1-2 CM MARGINS

• ADVENTITIA OR PERINEURIUM SHOULD BE REMOVED IF NEUROVASCULAR

INVOLVEMENT

• AMPUTATION VS LIMB SALVAGE VS EN BLOC RESECTION

• BONE INVOLVEMENT OCCUR IN <5% AND ASSOCIATED WITH DECREASED

SURVIVAL AND IS MANAGED THROUGH BONE RESECTION
LOCOREGIONAL LYMPHADENECTOMY

• <5% HAVE LN METS

• BIOPSY BEFORE LYMPHADENECTOMY

• U/S GUIDED FNAC OR CNB

• IMPROVED SURVIVAL FOR PATIENTS WITH ISOLATED REGIONAL LYMPH

NODE METASTASES TREATED WITH RADICAL LYMPHADENECTOMY

• SENTINEL LYMPH NODE BIOPSY

 AMPUTATION

• AMPUTATION IS THE TREATMENT OF CHOICE FOR THE 5% OF PATIENTS

• AMPUTATION VS LIMB SALVAGE (LOCAL RESECTION + RADIATION)

• ISOLATED REGIONAL PERFUSION

• TNF AND MELPHALAN IN HYPERTHERMIC CONDITIONS(40ºC FOR 90MINUTES)
 RADIATION THERAPY
• STANDARD TREATMENT FOR HIGH GRADE EXTREMITY AND TRUNK
WALL SOFT TISSUE SARCOMAS EITHER IN THE PRE- OR POSTOPERATIVE
SETTING.
• DIFFERENT TYPE OF THERAPY
• EXTERNAL-BEAM RADIATION THERAPY
• BRACHYTHERAPY
• INTENSITY-MODULATED RADIATION THERAPY (IMRT)

• RADIATION MARGIN IS 5-7 CM IS USED AS STANDARD BUT FOR LARGER

TUMORS IT CAN GO AS LARGE AS 15CM
• PRE-OP VS POST OP RADIATION THERAPY
• PRE-OP(50GY): SHRINKS TUMOR SIZE, TISSUE BED UNDISTURBED, SMALLER DOSE BUT
DIFFICULTY ASSESSING MARGINS AND INCREASED RATE OF POST OP WOUND COMPLICATION
• POST-OP(60-70GY): HIGHER DOSE HENCE RADIATION TOXIC EFFECTS
• SIMILAR RECURRENCE AND PROGRESSION FREE SURVIVAL
RADIATION THERAPY

• PRE-OP RADIATION: THE MOST FREQUENT WOUND COMPLICATIONS ARE

WOUND DEHISCENCE, WOUND NECROSIS, PERSISTENT DRAINAGE, INFECTION,
SEROMA FORMATION, ULCERATION, AND CELLULITIS

• PRE-OP RADIATION > POST OP RADIATION FOR WOUND WITH FREE FLAPS

• LONG TERM EFFECTS OF RADIATION: FIBROSIS/CONTRACTURES,

LYMPHEDEMA, NEUROLOGIC INJURY, OSTITIS AND FRACTURES

• FACTORS FOR POOR FUNCTIONAL OUTCOME: LARGE TUMOR, HIGHER

DOSES, LONGER RADIATION FIELDS, POOR TECHNIQUE, NEURAL SACRIFICE, POST
OP FRACTURES AND WOUND COMPLICATION
SYSTEMIC THERAPY

• CHEMO SENSITIVE-
SYNOVIAL SARCOMA, ROUND CELL LIPOSARCOMA, UTERINE
LEIOMYOSARCOMA

• INTERMEDIATE-
EPITHELIOID SARCOMA, MYXOFIBROSARCOMA, PLEOMORPHIC
LIPOSARCOMA, CLEAR CELL, ANGIOSARCOMA, DESMOPLASTIC ROUND CELL TUMORS

• CHEMO RESISTANT-CLEAR
CELL, ALVEOLAR SOFT PART SARCOMA, ENDOMETRIAL
STROMAL SARCOMA, MYXOID CHONDROSARCOMA

• DOXORUBICIN AND IFOSFAMIDE ARE TWO MOST ACTIVE AGENTS

• DOXORUBICIN-CARDIOTOXIC
• IFOSFAMIDE- HAEMORRHAGIC CYSTITIS, NEUROTOXICITY, RTA

• NOVEL CHEMOTHERAPEUTIC AGENTS AND TARGETED THERAPY

SYSTEMIC THERAPY

• NEOADJUVANT VS ADJUVANT CHEMOTHERAPY

• NEOADJUVANT GIVES AN INSIGHT HOW THE TUMOR WILL RESPOND TO
ADJUVANT THERAPY
• ADVANTAGE FOR NEOADJUVANT- SHRINKS THE TUMOR FOR SURGERY ENABLING
LESS MORBID SURGERY
• DISADVANTAGE- MYELOSUPPRESSION AND POST OP WOUND COMPLICATION

• CONCURRENT CHEMO AND RADIOTHERAPY HAVE IMPROVED DISEASE FREE

SURVIVAL BY TREATING MICROSCOPIC DISEASE AND ENHANCING
TREATMENT OF MACROSCOPIC DISEASE
POST TREATMENT SURVEILLANCE

• HX, P/E AND CHEST CT OR RADIOGRAPH EVERY 3-6MONTHS FOR 2-3 YEARS
AFTER COMPLETION OF TREATMENT

• ANNUALLY YEARS 2-5

• TUMOR SITE EVERY 6 MONTHS PREFERABLY BY MRI FOR EXTREMITY AND CT

FOR INTRA-ABDOMINAL OR RETROPERITONEAL TUMORS

• FOR RECURRENCE- CT EVERY 3- 6 MONTHS FOR THE FIRST 2 YEARS, THEN

EVERY 6 MONTHS FOR 3 YEARS
MANAGEMENT OF RECURRENT SARCOMA
• 20%= LOCAL RECURRENCE FOR EXTREMITY SARCOMA ACCOMPANIED BY
DISTANT METASTASIS

• PATIENTS WITH MICRO METS ARE AT RISK OF RECURRENCE

• MEDIAN TIME TO LOCAL RECURRENCE IS 16 MONTHS(65% IN 2 YEARS AND 90% IN

4 YEARS)

• ISOLATED LOCAL RECURRENCE SHOULD BE TREATED WITH AGGRESSIVE

RESECTION WITH NEGATIVE MARGIN- AMPUTATION

• 1º DETERMINANT OF SURVIVAL- DISTANT METASTASIS

MANAGEMENT OF DISTANT
METASTASIS(SURGERY)
• SURGICAL RESECTION AS A PALLIATIVE TREATMENT

• SELECTED PATIENTS MAY BECOME LONG-TERM SURVIVORS AFTER PULMONARY

RESECTION (15-40% ARE LONG TERM SURVIVIOURS)
• LESS THAN FOUR NODULES,
• LONG DISEASE-FREE INTERVALS, AND
• NO ENDOBRONCHIAL INVASION

• 5 YEAR SURVIVAL AFTER METASTATECTOMY IS 38%

• FAVOURABLE PROGNOSTIC FACTORS

• TUMOR FREE MARIGIN
• AGE<40
• GRADE 1 OR 2 TUMOR
MANAGEMENT OF DISTANT METASTASIS
(CHEMO&RADIATION)

• DOXORUBICIN, EITHER ALONE OR COMBINED WITH OTHER AGENTS

• FACTORS PREDICTING BETTER OUTCOME FOR CHEMOTHERAPY

• GOOD PERFORMANCE STATUS,
• PREVIOUS RESPONSE TO CHEMOTHERAPY,
• YOUNGER AGE,
• ABSENCE OF HEPATIC METASTASES,
• LOW-GRADE TUMOR,
• LONG DISEASE-FREE INTERVAL

• RADIATION DOSES GREATER THAN 63 GY YIELDED SUPERIOR TUMOR CONTROL, BUT

DOSES GREATER THAN 68 GY RESULTED IN INCREASED RATES OF MAJOR
COMPLICATIONS
SPECIAL CLINICAL SITUATION
• RETROPERITONEAL SARCOMA
• 1/3 OF SOFT TISSUE SARCOMA AND MOST ARE MALIGNANT
• LIPOSARCOMA AND LEIOMYOSARCOMA ARE MOST COMMON TYPE
• 70% ARE >10CM AT DIAGNOSIS
• PRESENTING SYMPTOMS: PAIN EARLY SATIETY AND OBSTRUCTIVE SYMPTOMS
• 11%- SYNCHRONOUS METS
• COMPLETE RESECTION IS TREATMENT OF CHOICE, EN BLOC RESECTION
• ADJUVANT CHEMOTHERAPY NOT HELPFUL AND RADIATION THERAPY IS SUGGESTED
• RECURS MORE OFTEN THAN EXTREMITY AND TRUNK SARCOMAS
• RECURRENCE MOSTLY ,METASTASIS TO LIVER IN ADDITION TO LUNGS AND
SARCOMATOSIS
• RECURRENCE HAVE A MORE POORLY DIFFERENTIATED PATHOLOGY FROM INITIAL
SARCOMA
GI SARCOMA

• SYMPTOMS ARE NON SPECIFIC

• BLEEDING, MASS, PAIN, EARLY SATIETY, DYSPEPSIA, TENESMUS, CHANGE IN BOWEL HABIT

• CT-HELPFUL BUT OTHER MALIGNANCIES POSSIBLE

NB LACK OF LN METS IS SUGGESTIVE
• ENDOSCOPY & BIOPSY TO R/O ADENOCARCINOMA
• TREATMENT
• RESECT WITH 2-4 CM FREE MARGIN
• NOT THE CASE ALL THE TIME(EG GEJ)
• SEGMENTAL BOWEL RESECTION
• SMALL RECTAL MASS → TRANSANAL EXCISION
 BREAST SARCOMA

• 1% OF BREAST CA AND 5% OF SARCOMAS

• CAN BE OF VARIETY OF HISTOLOGY TYPES

• ANGIOSARCOMA ACCOUNTS 50% ASSOCIATED WITH RADIATION THERAPY FOR

BREAST CA

• CAN BE 3-20 YEARS AFTER RADIATION

• PUNCH /INCISIONAL BIOPSY IS DIAGNOSTIC

• COMPLETE EXCISION WITH NEGATIVE MARGIN +/- NEOADJUVANT , MASTECTOMY

AND LYMPHADENECTOMY NOT NEEDED IN CASES OF PHYLLOIDS
UTERINE SARCOMA

• UTERINE LEIOMYOSARCOMA-
• ACCOUNTS FOR 35-40%
• MORE COMMON IN 50-60S
• TAH,BSO DEPENDS ON PTS WILL
• NO LYMPHADENECTOMY
• ADJUVANT RADIATION FOR HIGH RISK PATIENTS

• ENDOMETRIAL STROMAL SARCOMA-

• 7-10% OF UTERINE SARCOMA
• GRADE BASED ON MITOTIC COUNT
• CLINICAL COURSE DEPENDS ON GRADE
• EXPRESS PROGESTERONE RECEPTOR
• TAH + BSO IN PREMENOPAUSAL
• ADJUVANT HORMONAL THERAPY
UTERINE SARCOMA
• MIXED MULLERIAN TUMOR
• 50% OF UTERINE SARCOMAS
• POSTMENOPAUSAL
• EPITHELIAL ORIGIN AND TREATED WITH AGENTS FOR OVARIAN & ENDOMETRIAL
CA
• UNDIFFERENTIATED ENDOMETRIAL SARCOMA
• AGGRESSIVE
• DOESN’T EXPRESS HORMONE RECEPTORS
• POOR PROGNOSIS EVEN WITH LOCALIZED DISEASE
• TAH +/- BSO WITH POST OP PELVIC RADIATION
• SYSTEMICAGENTS FOR RECURRENT OR METS
DESMOIDS
• NOT LOW GRADE, LOCALLY AGGRESSIVE BUT NO METS

• 50% ON EXTREMITIES, THE REST ON TRUNK& RP

• CAN BE ASSOCIATED WITH PREGNANCY, FAP

• RX→ WIDE RESECTION BUT 1/3 RECURRENCE EVEN AFTER RESECTION AND NO
RECURRENCE IN 2/3 EVEN AFTER +VE MARGIN RESECTION

• FUNCTION PRESERVING SURGERY(-/+MARGIN) + RADIATION

• METHOTREXATE + VINBLASTIN, DOXORUBICIN AND SORAFENIB, TAMOXIFEN, NSAIDS

 DFP

• LOW GRADE, NON METASTATIC, LOCALLY AGGRESSIVE

• MOSTLY ON TRUNK(40%), HEAD, NECK, EXTREMITY

• NODULAR, CUTANEOUS, SLOWLY GROWING MASS

• TREATMENT→ WIDE LOCAL EXCISION

-ONLY 10% RECURRENCE

• TRANSLOCATION OF CHROMOSOMES 17&22 →ACTIVATION OF PDGFR/TYROSINE KINASE→

PROMOTES ITS GROWTH.

• IMATINIB IS EFFECTIVE IN NON RESECTABLE CASES

GIST

• 80% HAVE MUTATION IN GENE ENCODING KIT RECEPTOR TYROSINE KINASE

AND 5-10% PDGFRA RECEPTOR TYROSINE KINASE

• STOMACH(60%), SMALL BOWEL(30%)

• NON SPECIFIC SYMPTOMS:

• PAIN
• SATIETY
• BLEEDING

• METASTASIS IS MOSTLY TO LIVER AND OR ABDOMINAL CAVITY

GIST

• LOCALIZED DISEASE-RESECTION WITH –VE MARGIN

• NO NEED OF LYMPHADENECTOMY, WIDE MARGIN
• TUMOR SIZE &MITOTIC ACTIVITY…PROGNOSTIC

• LOCALLY ADVANCED OR METS-IMATINIB (INHIBITOR OF KIT PROTEIN TK)

• OPTIMAL DURATION, LONG TERM TOXICITY...UNCERTAIN
• MANY PTS DEVELOP RESISTANCE(1º = WITH IN 6 MONTHS OR 2º = AFTER 6
MONTHS)
• IF RESISTANCE DEVELOP EITHER ESCALATE THE DOSE OR CHANGE TO SECOND
LINE (SUNITINIB)
• IF IMATINIB AND SUNITINIB RESISTANT THEN GO FOR REGORAFENIB
• IF HIGH RISK FOR RECURRENCE-36MONTHS OF IMATINIB
 PAEDIATRIC SARCOMA

• RHABDOMYOSARCOMA VS NON RHABDOMYOSARCOMA

• RHABDOMYOSARCOMA-MOST COMMON SOFT TISSUE TUMOR IN <15 AGE GROUP.
• DISTRIBUTION
• GENITOURINARY (24%)
• EXTREMITIES (20%)
• HEAD & NECK(20%)
• PARAMENINGEAL (16%)
• HISTOLOGY: EMBRYONAL(70%)& ALVEOLAR(20%)
• HAVE DIFFERENT TRANSLOCATIONS HAVE COMMON DOWNSTREAM TARGETS
LIKE P53&RB PATHWAYS
PAEDIATRIC SARCOMA

• COMPLETE RESECTION WITH –VE (GI) OR +VE (GII) MARGINS HAVE OVERALL
SURVIVAL CLOSE TO 90% WITH SYSTEMIC THERAPY

• DON’T RESECT GENITOURINARY AND HEAD & NECK

• CHEMO ALONE HAS GOOD CONTROL FOR SUCH ONES

• SLNB IS IMPORTANT B/C HIGH PROPENSITY FOR LN METASTASIS(20-30%)

• MOST PRESENT WITH METS TO THE LUNGS, BONE MARROW AND BONE CHEMO IS
RECOMMENDED FOR ALL
PAEDIATRIC SARCOMA
• NONRHABDOMYOSARCOMA(60% OF SOFT TISSUE SARCOMA)
CATEGORIES A-FIBROSARCOMA B KAPOSI SARCOMA
C-SPECIFIED D UNSPECIFIED

• APPROACH IS SIMILAR TO ADULTS

• H&P→ IMAGING→ CORE NEEDLE BIOPSY

• SURGERY IS MAINSTAY OF TREATMENT

• RADIATION FOR HIGH GRADE

THANK YOU