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MESENCHYMAL TUMORS
Eva SZEKANECZ M.D.,Ph.D.Inst. Oncology MHSC Debrecen
2013
MESENCHYMAL TUMORS
• nem csírasejt
} eredetű támasztószövetből• nem ivarlemez
Markers of mesenchymal differentiation:
1. Vimentin
2. Desmin
3. Aktin
4. MyoD1
5. Myoglobin
6. Myogenin
7. p63
INTRODUCTION
• 0.5-1% of malignant solid tumors• more frequent in childhood, but can be seen in
any age-group (7%)1. leukemias
2. CNS tumors
3. lymphomas
4. soft tissue sarcomas
• equal in both sexes• poor prognosis: local recurrency: 30-60% after
primary removal• distant metastasis within 5 ys: 40-60%
ETIOLOGY
• NOT EXACTLY KNOWN!harci gázok, conservants, gyomirtó, former radiation therapy, foreign body inclusion, chronic lymphoedema, viral infection, immun-deficiency, traumas (?)
• genetic: in some sarcomas genetic malformations and mutations are proven:
GIST: c-kit protoonkogen mutation PNET: t(11;22), q(24;12) reciprok
translocation retinoblastoma gene (13q14) allel lost
GENERAL FEATURES
• NOT A FORMER BENIGN TUMOR BECOMES MALIGNANT!
• origin: from any non-lymphoid, or haemopoetic mesodermal tissue - EXCEPTnerve(bone, cartilage, fat, muscle, tendon, connective tissue, vessels)50% the mass of the body is extraskeletal
• locally agressive growth• fast progression (it correlates with the histological
grade of the tumor tissue)• it’s difficult to treat them (lethal within a year
without oncotherapy)
LOCALISATION
more than half of the cases: on limbs
• LOWER LIMB 43-47% 75% above the knee
• retroperitoneal 20-25%• upper limb 13-16%• chest/ trunk 15-17%• head and neck 8%• breast 1%
EPIDEMIOLOGYSOFT TISSUE SARCOMAS
mainly mesodermal tumors (skeletal and extraskeletal connective tissues!)
• direct spread along muscles and fascias • most frequent in adults: liposarcoma (synovial
sarcoma 10%)
in childhood: rhabdomyosarcoma• sporadic ( but very rarely, it can be familial!)
• poor prognosis: recurrency rate after primary excision within 5 ys: 30-60%,
distatant met. within 2 ys: 40-60%
•hematogenic spread: lungs, liver, bones
SURGICAL TREATMENT
• Its’ success is still doubtful…
• en bloc resection of the involved compartment has still have priority
• or: marginal resection widely: 2-3 cm safety marginal zone
• Survival: 4 ys after radical ST2 ys after incomplete resection
• Surgury of met.-s: lymph node dissection (block ~)metastasectomy (lungs)
• Interventional chemotherapy: regional haemofiltration
IRRADIATION
• TELETHERAPY /BRACHYTHERAPY
• the highest dose as possible• 1.8 -2 Gy/ day
• Setting:preoperative, intraoperative, postoperative, palliative
• Side effects: (10-24 months) skin/muscle fibrosis dysfunction of joints lymphedema tunnel syndrome paresthesia, kinetic
problems
OSTEOSARCOMAS
• very rare: 0.2-0.5%• more frequent in children (4.-5.hely)
• 35% osteosarcoma• 25% chondrosarcoma• 16% Ewing sarcoma/PNET
• 8% chordoma• 5% MFH
CLINICAL SYMPTOMS
• PAIN• SWELLING ( the circumference of the limb increases)• hypercoloration due to soft tissue involvement • hyperaemia on skin• sometimes fever (hyperpyrexia is poor prognostic value!)• loss of moves• pathologic fracture (1%)• reactive synovitis of the neighbouring joint
• X-ray: Codmann triangle, skip metastasis• pathology: microscopically infiltrative (even it seemed to be
encapsulated, macroscopically!)
PROGNOSTIC FACTORS
postop. survival is better if:• distant from the trunk of body• chemosensitivity• ablastic surgery (resection margin?)• less, than 20%- intratumoral cartilage ratio• less, than 60 cm3- tumor size• lower grade
• mdm2 producing• P-glicoprotein producing
EPIDEMIOLOGY OSTEOSARCOMAS
• new cases: 1,5 (EU), - 8 (USA) /1 000 000 /year• 2:1 ffi/nő• bimodal age distribution: mainly younger than
20 ys (Ewing sc.) and above 60 ys (Paget kór)• 1st peak:adolescents – 8% of all malignancies of
the youth• predilective localisations: from the metaphysis of
the tubular long bones, through the … cartilage to the epiphysis
• grows on the surface• 80% around the knees - direct articular or
pericapsular spread
CLASSIFICATION OF OSTEOSARCOMAS
• primer OSC: from a hidden bone-disease
• secunder OSC: on an abnormal bone, because of a carcinogen effect
CHONDROSARCOMA
• 2nd most frequent primary bone tumor
• 25% of all bone tumors• in adults (3rd-7th decade)• 10-12 new cases/ 10M/ year• hyalinic differentiation• slow growth• 1st: PELVIC REGION
+femur, humerus, tibia, ribs• distant met.: 10%• Th: surgical+ irradiation• (radio-, and chemo resistency)• Surgery: palliatív debulking or
radical amputation
EEWING SARCOMA / PNETWING SARCOMA / PNET
• 3rd mst frequent bone sarcoma
• 6-8% of malignant bone tumors
• 3-4 new case/10M/year• highly malignant:
dedifferentiated cellsneuroectodermalis?mesenchymalis
stem cell origin?• children/adolescent (80%
between 5-15 ys) • very rare over30 ys of age• PAS+, CD99+,• translocation (t22)
BONE METASTASES
• 3/10 000• rather multiplied
• osteolytic /osteoplastic
• Breast cancer• Lung cancer• Prostate cancer• Thyroid cancer
differential diagnosis !!!
COMBINED THERAPEUTIC SCHEME
Biopsy → neoadjuvant chemoth. → surgery → adjuvant chemoth.
limb preserving / amputation
(65-75%)
RR : 75-85%
loc. reurrency 2-9%
SURGICAL TREATMENT• excochleation (?)• resection
• resection with wide margins –limb preserving intent (60-75%)
• radical amputation
• Palliative:osteosynthesis stabilisation – to avoid pathological fractures
RADIOTHERAPY• mainly radioresistent tumors
more sensitive: Ewing sarcoma, MFH
• Neutron irradiation (?) – lots of side effects
• there’s no prophylactic indication !!!!
• if the surgical margins are positive: 50-60 Gy
• palliative intent to treat regional or distant met.-s
• combined chemo-radiation
• lots of organs to protect!!!
DRUDGS USED IN TREATMENT OF SARCOMAS
• Ifosfamid• Adriamycin, Epiadriamycin• cisplatinum
• dacarbazien ↓ RR• vepesid
• raltitrexed• gemcitabin
THERAPEUTIC SCHEMES
• COSS protocol – 9 ws neoadjuvant chemo, surgery on the 10th week +14 ws adjuvant chemo
• CYVADIC 30%• MAID 40%• VIP 45%• EWING• MAP
– taxanes– topothecan– vinorelbin– gemcitabin– temozolamide