MESENCHYMAL TUMORS Eva SZEKANECZ M.D.,Ph.D. Inst. Oncology MHSC Debrecen 2013.

MESENCHYMAL TUMORS

Eva SZEKANECZ M.D.,Ph.D.Inst. Oncology MHSC Debrecen

2013

MESENCHYMAL TUMORS

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} 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